Документ 2368360

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ɈȽɅȺȼɅȿɇɂȿ
ȼȼȿȾȿɇɂȿ……………………………………………………………3
1. ɉɊɈɌȿɈɆɂɄȺ ɂ ɉɈɌȿɇɐɂȺɅ ɋɌȼɈɅɈȼɕɏ ɄɅȿɌɈɄ
ȾɅə ɌȿɊȺɉɂɂ ȺɌȿɊɈɋɄɅȿɊɈɁȺ………………………………9
1.1. ɉɪɨɬɟɨɦɢɤɚ ɤɚɤ ɢɧɫɬɪɭɦɟɧɬ ɢɡɭɱɟɧɢɹ ɤɥɟɬɨɤ…………………... 9
1.2. ɋɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ, ɚɬɟɪɨɫɤɥɟɪɨɡ ɢ ɩɪɨɬɟɨɦɢɤɚ.……………..14
1.3. Ƚɟɦɨɩɨɷɬɢɱɟɫɤɢɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ ɤɚɤ ɨɛɴɟɤɬ
ɢɫɫɥɟɞɨɜɚɧɢɹ ɢ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɜ ɩɚɬɨɮɢɡɢɨɥɨɝɢɢ…………. 19
1.3.1. Ɋɟɝɭɥɹɬɨɪɵ ȽɋɄ………………………………………………21
1.3.2. Ⱥɥɶɬɟɪɧɚɬɢɜɧɵɟ ɢɫɬɨɱɧɢɤɢ ȽɋɄ……………………………23
1.3.3. Ʉɥɢɧɢɱɟɫɤɚɹ ɷɮɮɟɤɬɢɜɧɨɫɬɶ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ…………..25
1.3.4. ɉɪɨɬɟɨɦɢɤɚ ȽɋɄ…………………………………………….. 27
2. ɆȺɌȿɊɂȺɅɕ ɂ ɆȿɌɈȾɕ…………………………………….. 35
2.1. Ʉɥɟɬɨɱɧɵɟ ɥɢɧɢɢ………………………………………………. 35
2.2. Ɇɨɧɨɧɭɤɥɟɚɪɧɵɟ ɤɥɟɬɤɢ………………………………………. 35
2.3. Ƚɟɦɨɩɨɷɬɢɱɟɫɤɢɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ (ȽɋɄ)……………………35
2.4. ȼɵɞɟɥɟɧɢɟ CD34+ ɫ ɩɨɦɨɳɶɸ ɦɚɝɧɢɬɧɵɯ ɫɮɟɪ………………37
2.5. Ʉɥɟɬɤɢ ɢɡ ɢɧɬɢɦɵ (ɦɟɞɢɢ) ɚɨɪɬɵ………………………………39
2.6. ɉɪɢɝɨɬɨɜɥɟɧɢɟ ɢ ɨɩɬɢɦɢɡɚɰɢɹ ɨɛɪɚɡɰɨɜ ɞɥɹ ɢɫɫɥɟɞɨɜɚɧɢɹ…. 42
2.7. ɉɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɶ (ɚɥɝɨɪɢɬɦ) ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ…….. 45
2.8. Ɋɚɡɞɟɥɟɧɢɟ ɛɟɥɤɨɜ ɫ ɩɨɦɨɳɶɸ ɞɜɭɦɟɪɧɨɝɨ ɝɟɥɶ-ɷɥɟɤɬɪɨɮɨɪɟɡɚ…47
2.9. Ɉɤɪɚɲɢɜɚɧɢɟ (ɞɟɬɟɤɰɢɹ) ɢ ɜɢɡɭɚɥɢɡɚɰɢɹ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ…… 48
2.10. Ⱥɧɚɥɢɡ ɢɡɨɛɪɚɠɟɧɢɣ ɢ ɢɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ……………. 48
2.11. Ⱥɧɚɥɢɡ ɞɜɭɦɟɪɧɵɯ ɝɟɥɟɣ……………………………………… 49
2.12. ȼɵɪɟɡɚɧɢɟ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ……………………………………49
2.13. ɉɟɪɟɜɚɪɢɜɚɧɢɟ ɛɟɥɤɚ ɬɪɢɩɫɢɧɨɦ…………………………… 51
2.14. Ɉɫɨɛɟɧɧɨɫɬɢ ɚɧɚɥɢɡɚ ɤɚɪɞɢɨɩɪɟɩɚɪɚɬɨɜ……………………52
2.15. ɂɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ – MALDI Mass Spec………………. 54
2.16. Ɉɛɴɟɞɢɧɟɧɢɟ ɞɚɧɧɵɯ, ɩɨɥɭɱɟɧɧɵɯ ɧɚ ɪɚɡɧɵɯ ɷɬɚɩɚɯ ɚɧɚɥɢɡɚ... 55
2.17. ɂɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ……………………………………….56
3. ɉɈɅɍɑȿɇɇɕȿ ɊȿɁɍɅɖɌȺɌɕ……………………………….. 59
3.1. ȼɥɢɹɧɢɟ ɩɚɪɚɬɢɪɟɨɢɞɧɨɝɨ ɝɨɪɦɨɧɚ ɧɚ ɨɫɬɟɨɛɥɚɫɬɵ…………59
3.2. Ⱥɧɚɥɢɡ ɩɪɨɬɟɨɦɚ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ………63
3.2.1. Ɇɨɧɨɧɭɤɥɟɚɪɧɵɟ ɤɥɟɬɤɢ …………………………………… 63
3.2.2. ɉɨɩɭɥɹɰɢɹ CD34+ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ….. 74
3.3. ɂɡɭɱɟɧɢɟ ɚɫɫɨɰɢɚɰɢɢ ɩɪɨɬɟɨɦɧɨɝɨ ɩɪɨɮɢɥɹ
ɫ ɚɬɟɪɨɫɤɥɟɪɨɡɨɦ………………………………………………....... 82
4. ɈȻɋɍɀȾȿɇɂȿ ɊȿɁɍɅɖɌȺɌɈȼ………………………………. 89
4.1. Ɋɟɚɤɰɢɹ ɩɪɨɬɟɨɦɚ ɨɫɬɟɛɥɚɫɬɨɜ ɧɚ ɩɚɪɚɬɢɪɟɨɢɞɧɵɣ ɝɨɪɦɨɧ.… 89
4.2. ɏɚɪɚɤɬɟɪɢɫɬɢɤɚ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ………. 92
4.2.1. Ȼɟɥɤɨɜɵɣ ɩɪɨɮɢɥɶ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɤɥɟɬɨɤ……………….92
4.2.2. Ȼɟɥɤɨɜɵɣ ɩɪɨɮɢɥɶ CD34+ ȽɋɄ………………………………96
4.3. ɉɪɨɬɟɨɦɢɤɚ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɢ ɩɟɪɫɩɟɤɬɢɜɵ ɢɫɩɨɥɶɡɨɜɚɧɢɹ
ȽɋɄ ɞɥɹ ɬɟɪɚɩɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ……………………………… 103
ȼɕȼɈȾɕ ……………………………………………………………..111
5 ɋɉɂɋɈɄ ɅɂɌȿɊȺɌɍɊɕ…………………………………………113
ɋɉɂɋɈɄ ɋɈɄɊȺɓȿɇɂɃ………………………………………… 127
ɉɊɂɅɈɀȿɇɂȿ………………………………………………………129
Ɍɚɛɥɢɰɚ 1…………………………………………………………… 129
Ɍɚɛɥɢɰɚ 2…………………………………………………………… 156
Ɍɚɛɥɢɰɚ 3…………………………………………………………… 176
Ɍɚɛɥɢɰɚ 4…………………………………………………………… 190
Ɍɚɛɥɢɰɚ 5…………………………………………………………… 205
Ɍɚɛɥɢɰɚ 6…………………………………………………………… 230
2
ȼȼȿȾȿɇɂȿ
Ⱥɤɬɭɚɥɶɧɨɫɬɶ ɬɟɦɵ ɢɫɫɥɟɞɨɜɚɧɢɹ ɨɩɪɟɞɟɥɟɧɚ, ɜɨ-ɩɟɪɜɵɯ, ɬɟɦ,
ɱɬɨ ɜ ɦɢɪɟ ɧɚɛɥɸɞɚɟɬɫɹ ɨɝɪɨɦɧɵɣ ɢɧɬɟɪɟɫ ɤ ɩɪɨɬɟɨɦɢɤɟ ɫɨ ɫɬɨɪɨɧɵ
ɛɢɨɦɟɞɢɰɢɧɵ ɤɚɤ ɞɥɹ ɪɚɧɧɟɝɨ ɨɛɧɚɪɭɠɟɧɢɹ ɢ ɦɨɧɢɬɨɪɢɧɝɚ ɛɨɥɟɡɧɟɣ,
ɬɚɤ ɢ ɞɥɹ ɪɚɡɪɚɛɨɬɤɢ ɛɨɥɟɟ ɷɮɮɟɤɬɢɜɧɵɯ ɦɟɬɨɞɨɜ ɥɟɱɟɧɢɹ ɧɚ ɨɫɧɨɜɟ
ɥɭɱɲɟɝɨ ɩɨɧɢɦɚɧɢɹ ɩɚɬɨɝɟɧɟɡɚ. ȼ ɩɨɫɥɟɞɧɢɟ ɝɨɞɵ ɬɟɯɧɨɥɨɝɢɢ ɞɥɹ
ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɩɪɨɬɟɨɦɚ ɡɧɚɱɢɬɟɥɶɧɨ ɭɫɨɜɟɪɲɟɧɫɬɜɨɜɚɥɢɫɶ ɛɥɚɝɨɞɚɪɹ ɛɨɥɶɲɟɣ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬɢ ɚɧɚɥɢɬɢɱɟɫɤɢɯ ɦɟɬɨɞɨɜ, ɢɫɩɨɥɶɡɭɸɳɢɯɫɹ ɜ ɧɢɯ. Ʉɪɨɦɟ ɬɨɝɨ, ɤɨɦɩɶɸɬɟɪɧɵɟ ɬɟɯɧɨɥɨɝɢɢ,
ɩɪɢɦɟɧɹɟɦɵɟ ɞɥɹ ɚɧɚɥɢɡɚ ɩɪɨɬɟɨɦɚ, ɫɬɚɥɢ ɛɨɥɟɟ ɦɨɳɧɵɦɢ, ɩɨɹɜɢɥɢɫɶ
ɛɢɨɢɧɮɨɪɦɚɬɢɱɟɫɤɢɟ ɢɧɫɬɪɭɦɟɧɬɵ, ɛɥɚɝɨɞɚɪɹ ɤɨɬɨɪɵɦ ɫɬɚɥɨ ɜɨɡɦɨɠɧɵɦ ɢɡɜɥɟɱɟɧɢɟ ɦɚɤɫɢɦɚɥɶɧɨɝɨ ɤɨɥɢɱɟɫɬɜɚ ɢɧɮɨɪɦɚɰɢɢ ɢɡ ɢɫɫɥɟɞɭɟɦɵɯ ɨɛɪɚɡɰɨɜ. Ⱦɚɧɧɵɟ ɬɟɯɧɨɥɨɝɢɢ ɩɨɡɜɨɥɹɸɬ ɜɵɛɪɚɬɶ ɛɟɥɤɨɜɵɟ ɛɢɨɦɚɪɤɟɪɵ, ɚɫɫɨɰɢɢɪɨɜɚɧɧɵɟ ɫ ɡɚɛɨɥɟɜɚɧɢɹɦɢ.
ȼɨ-ɜɬɨɪɵɯ, ɩɪɨɬɟɨɦɢɤɚ ɩɨɡɜɨɥɹɟɬ ɩɪɨɜɟɫɬɢ ɬɳɚɬɟɥɶɧɵɣ ɚɧɚɥɢɡ
ɛɟɥɤɨɜ ɜ ɨɛɥɚɫɬɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɣ ɫɨɫɭɞɢɫɬɨɣ ɬɤɚɧɢ ɢ ɨɛɧɚɪɭɠɢɬɶ ɜɢɞɵ ɛɟɥɤɨɜ, ɤɨɬɨɪɵɟ ɭɱɚɫɬɜɭɸɬ ɜ ɫɨɫɭɞɢɫɬɨɦ ɪɟɦɨɞɟɥɢɪɨɜɚɧɢɢ
ɢ ɚɬɟɪɨɝɟɧɟɡɟ. ɂɞɟɧɬɢɮɢɤɚɰɢɹ ɱɟɥɨɜɟɱɟɫɤɨɝɨ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ
ɩɪɨɬɟɨɦɚ ɛɭɞɟɬ ɫɥɭɠɢɬɶ ɮɭɧɞɚɦɟɧɬɨɦ ɞɥɹ ɞɚɥɶɧɟɣɲɢɯ ɢɫɫɥɟɞɨɜɚɧɢɣ,
ɩɨɦɨɝɚɹ ɩɨɫɬɪɨɢɬɶ ɢ ɩɪɨɜɟɪɢɬɶ ɧɨɜɵɟ ɝɢɩɨɬɟɡɵ.
ȼ-ɬɪɟɬɶɢɯ, ɧɟɞɚɜɧɢɟ ɤɥɢɧɢɱɟɫɤɢɟ ɢɫɫɥɟɞɨɜɚɧɢɹ ɩɨɤɚɡɵɜɚɸɬ, ɱɬɨ
ɧɟɞɢɮɮɟɪɟɧɰɢɪɨɜɚɧɧɵɟ ɤɥɟɬɤɢ, ɰɢɪɤɭɥɢɪɭɸɳɢɟ ɜ ɤɪɨɜɨɬɨɤɟ, ɢɦɟɸɬ
ɨɝɪɨɦɧɵɣ ɩɨɬɟɧɰɢɚɥ ɞɥɹ ɪɟɝɟɧɟɪɚɰɢɢ ɫɨɫɭɞɢɫɬɨɣ ɬɤɚɧɢ. Ɉɧɢ ɩɚɬɪɭɥɢɪɭɸɬ ɨɪɝɚɧɢɡɦ ɢ ɫɬɟɤɚɸɬɫɹ ɤ ɦɟɫɬɭ, ɝɞɟ ɨɛɧɚɪɭɠɢɜɚɸɬ ɩɨɜɪɟɠɞɟɧɢɟ ɫɨɫɭɞɚ. ɉɨɹɜɥɹɸɬɫɹ ɢ ɧɨɜɵɟ ɞɚɧɧɵɟ ɨɛ ɭɱɚɫɬɢɢ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ
ɤɚɤ ɝɟɦɨɩɨɷɬɢɱɟɫɤɨɣ, ɬɚɤ ɢ ɫɬɪɨɦɚɥɶɧɨɣ ɥɢɧɢɣ ɞɢɮɮɟɪɟɧɰɢɪɨɜɤɢ, ɜ
ɚɬɟɪɨɝɟɧɟɡɟ. ɗɬɢ ɞɚɧɧɵɟ ɩɨɡɜɨɥɢɥɢ ɩɪɟɞɩɨɥɨɠɢɬɶ, ɱɬɨ ɜɚɠɧɵɦ ɦɨ3
ɦɟɧɬɨɦ ɜ ɪɚɡɜɢɬɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɹɜɥɹɟɬɫɹ ɩɪɨɧɢɤɧɨɜɟɧɢɟ ɤɨɥɨɧɢɟɨɛɪɚɡɭɸɳɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɜ ɢɧɬɢɦɭ ɜ ɦɟɫɬɚɯ ɤɨɧɰɟɧɬɪɚɰɢɢ ɥɢɩɢɞɨɜ. ɉɪɨɬɟɨɦ ɛɨɥɶɲɢɧɫɬɜɚ ɬɚɤɢɯ ɤɥɟɬɨɤ ɤ ɧɚɫɬɨɹɳɟɦɭ ɜɪɟɦɟɧɢ ɢɡɭɱɟɧ ɧɟɞɨɫɬɚɬɨɱɧɨ ɢ ɦɚɥɨɢɡɜɟɫɬɧɨɣ ɨɫɬɚɟɬɫɹ ɟɝɨ ɫɜɹɡɶ ɫ ɩɚɬɨɥɨɝɢɱɟɫɤɢɦɢ ɫɨɫɬɨɹɧɢɹɦɢ ɫɨɫɭɞɨɜ. ȼɢɞɢɦɨ, ɩɟɪɫɩɟɤɬɢɜɟɧ ɢ ɩɨɢɫɤ ɩɨɞɯɨɞɨɜ
ɤ ɫɬɢɦɭɥɹɰɢɢ ɪɟɝɟɧɟɪɚɬɢɜɧɨ-ɢɧɞɭɤɰɢɨɧɧɵɯ ɫɜɨɣɫɬɜ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ
ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ (ȽɋɄ), ɜɨɡɪɚɫɬɚɟɬ ɢɧɬɟɪɟɫ ɤ ɩɨɬɟɧɰɢɚɥɶɧɨɦɭ ɢɫɩɨɥɶɡɨɜɚɧɢɸ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ ɜ ɤɚɱɟɫɬɜɟ ɢɫɬɨɱɧɢɤɚ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɞɥɹ ɥɟɱɟɧɢɹ ɪɹɞɚ ɡɚɛɨɥɟɜɚɧɢɣ.
ȼ ɷɬɨɣ ɫɜɹɡɢ ɰɟɥɶɸ ɢɫɫɥɟɞɨɜɚɧɢɹ ɫɬɚɥɢ ɤɚɤ ɪɚɫɲɢɮɪɨɜɤɚ, ɧɚ ɨɫɧɨɜɟ ɭɫɨɜɟɪɲɟɧɫɬɜɨɜɚɧɧɨɝɨ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ, ɛɟɥɤɨɜɵɯ ɩɪɨɮɢɥɟɣ ȽɋɄ ɢɡ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ, ɬɚɤ ɢ ɜɵɹɜɥɟɧɢɟ ɚɫɫɨɰɢɚɰɢɢ ɦɟɠɞɭ
ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɦɢ ɩɨɪɚɠɟɧɢɹɦɢ ɢ ɩɪɨɬɟɨɦɧɵɦɢ ɩɪɨɮɢɥɹɦɢ ɢɧɬɢɦɵ ɢ ɦɟɞɢɢ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ ɞɥɹ ɩɨɧɢɦɚɧɢɹ ɩɨɬɟɧɰɢɚɥɶɧɵɯ ɜɨɡɦɨɠɧɨɫɬɟɣ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ȽɋɄ ɜ ɬɟɪɚɩɢɢ ɫɨɫɭɞɢɫɬɵɯ ɩɚɬɨɥɨɝɢɣ.
ȼ ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɞɚɧɧɨɣ ɰɟɥɶɸ ɜ ɪɚɛɨɬɟ ɪɟɲɚɸɬɫɹ ɫɥɟɞɭɸɳɢɟ
ɡɚɞɚɱɢ:
1. Ɉɩɬɢɦɢɡɢɪɨɜɚɬɶ ɚɥɝɨɪɢɬɦ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ, ɬɨ ɟɫɬɶ ɫɨɡɞɚɬɶ ɟɞɢɧɭɸ ɫɯɟɦɭ ɢɫɫɥɟɞɨɜɚɧɢɹ ɛɟɥɤɨɜɵɯ ɩɪɨɮɢɥɟɣ, ɤɨɬɨɪɚɹ ɭɩɪɨɳɚɥɚ ɛɵ ɫɪɚɜɧɟɧɢɟ ɞɚɧɧɵɯ, ɩɨɥɭɱɟɧɧɵɯ ɧɚ ɬɚɤɢɯ ɪɚɡɧɵɯ ɨɛɴɟɤɬɚɯ,
ɤɚɤ ɨɫɬɟɨɛɥɚɫɬɵ, ɦɨɧɨɧɭɤɥɟɚɪɧɵɟ ɤɥɟɬɤɢ (ɆɇɄ), CD34+ ȽɋɄ ɢ ɢɧɬɢɦɨ-ɦɟɞɢɚɥɶɧɵɣ ɫɥɨɣ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ.
2. ɂɡɭɱɢɬɶ ɫ ɩɨɦɨɳɶɸ ɩɪɨɬɟɨɦɢɤɢ ɩɨɜɟɞɟɧɢɟ ɛɟɥɤɨɜ ɨɫɬɟɨɛɥɚɫɬɨɜ, ɹɜɥɹɸɳɢɯɫɹ ɜɚɠɧɵɦ ɤɨɦɩɨɧɟɧɬɨɦ ɧɢɲɢ ȽɋɄ ɢ ɢɡɦɟɧɹɸɳɢɯɫɹ
ɩɨɞ ɞɟɣɫɬɜɢɟɦ ɩɚɪɚɬɢɪɟɨɢɞɧɨɝɨ ɝɨɪɦɨɧɚ.
3. ɉɪɨɜɟɫɬɢ ɢɞɟɧɬɢɮɢɤɚɰɢɸ ɛɟɥɤɨɜ, ɩɪɢɫɭɬɫɬɜɭɸɳɢɯ ɜ ɆɇɄ,
CD34+ ȽɋɄ, ɚ ɬɚɤɠɟ ɧɨɪɦɚɥɶɧɵɯ ɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɬɤɚɧɹɯ
ɚɨɪɬɵ.
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4. ɋɪɚɜɧɢɬɶ ɩɪɨɬɟɨɦɧɵɟ ɩɪɨɮɢɥɢ ȽɋɄ ɢɡ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ, ɢɧɬɢɦɵ ɢ ɦɟɞɢɢ ɫɨɫɭɞɨɜ ɜ ɩɪɨɰɟɫɫɟ ɚɬɟɪɨɝɟɧɟɡɚ. ȼɵɹɜɢɬɶ ɛɟɥɤɢ, ɭɪɨɜɧɢ
ɤɨɬɨɪɵɯ ɢɡɦɟɧɹɸɬɫɹ ɩɪɢ ɪɚɡɜɢɬɢɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ ɩɨɪɚɠɟɧɢɹ ɜ
ɢɧɬɢɦɨ-ɦɟɞɢɚɥɶɧɨɦ ɫɥɨɟ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ.
Ɉɛɴɟɤɬɚɦɢ ɢɫɫɥɟɞɨɜɚɧɢɹ ɛɵɥɢ ɢɡɛɪɚɧɵ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ, ɜ ɨɫɧɨɜɧɨɦ ɷɬɨ ɛɵɥɢ ɆɇɄ, ɩɨɩɭɥɹɰɢɹ ɤɥɟɬɨɤ CD34+ȽɋɄ,
ɨɱɢɳɟɧɧɵɯ ɢ ɜɵɞɟɥɟɧɧɵɯ ɢɡ ɨɛɪɚɡɰɨɜ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ, ɨɫɬɟɨɛɥɚɫɬɵ, ɚ ɬɚɤɠɟ ɛɟɥɤɢ ɢɡ ɢɧɬɢɦɵ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ ɢ ɛɟɥɤɢ ɢɡ ɦɟɞɢɢ ɭɱɚɫɬɤɨɜ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ ɤɚɤ ɧɟ ɩɨɪɚɠɟɧɧɵɯ ɚɬɟɪɨɫɤɥɟɪɨɡɨɦ, ɬɚɤ ɢ ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɯ ɪɚɡɥɢɱɧɵɦ ɜɢɞɚɦ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɩɨɪɚɠɟɧɢɣ.
ɇɚɭɱɧɚɹ ɧɨɜɢɡɧɚ ɨɛɴɹɫɧɹɟɬɫɹ ɬɟɦ, ɱɬɨ ɭɬɨɱɧɟɧɵ ɞɚɧɧɵɟ ɨ ɛɟɥɤɚɯ, ɜɵɞɟɥɟɧɧɵɯ ɢɡ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɛɥɹɲɟɤ ɢ ɩɪɟɬɟɪɩɟɜɚɸɳɢɯ
ɢɡɦɟɧɟɧɢɟ ɜ ɚɪɬɟɪɢɚɥɶɧɵɯ ɢɧɬɢɦɟ ɢ ɦɟɞɢɢ ɩɪɢ ɪɚɡɜɢɬɢɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɩɨɪɚɠɟɧɢɣ. ɂɞɟɧɬɢɮɢɰɢɪɨɜɚɧɵ ɦɧɨɝɢɟ ɛɟɥɤɢ ȽɋɄ ɢɡ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ ɫ ɭɱɟɬɨɦ ɢɯ ɜɧɭɬɪɢɤɥɟɬɨɱɧɨɣ ɥɨɤɚɥɢɡɚɰɢɢ, ɚ ɬɚɤɠɟ
ɩɪɨɬɟɨɦ ɨɫɬɟɨɛɥɚɫɬɨɜ ɜ ɞɢɧɚɦɢɤɟ. ɉɨɷɬɨɦɭ ɩɨɥɭɱɟɧɧɵɟ ɧɚɦɢ ɪɟɡɭɥɶɬɚɬɵ ɢɦɟɸɬ ɜɵɫɨɤɭɸ ɫɬɟɩɟɧɶ ɧɨɜɢɡɧɵ.
ɂɫɫɥɟɞɨɜɚɧɢɟ ɜɤɥɸɱɚɟɬ ɪɚɡɪɚɛɨɬɤɭ ɨɪɢɝɢɧɚɥɶɧɨɝɨ ɦɟɬɨɞɢɱɟɫɤɨɝɨ ɩɨɞɯɨɞɚ ɤ ɜɵɹɜɥɟɧɢɸ ɛɟɥɤɨɜɵɯ ɩɪɨɮɢɥɟɣ ȽɋɄ, ɚɪɬɟɪɢɚɥɶɧɨɣ ɢɧɬɢɦɵ ɢ ɦɟɞɢɢ ɧɚ ɪɚɧɟɟ ɧɟɞɨɫɬɢɠɢɦɨɦ ɭɪɨɜɧɟ, ɩɨɡɜɨɥɹɸɳɟɦ ɥɭɱɲɟ
ɩɨɧɹɬɶ ɢɯ ɫɥɨɠɧɭɸ ɩɪɢɪɨɞɭ.
Ɍɟɨɪɟɬɢɱɟɫɤɚɹ ɢ ɩɪɚɤɬɢɱɟɫɤɚɹ ɡɧɚɱɢɦɨɫɬɶ ɪɚɛɨɬɵ ɜɵɪɚɠɚɟɬɫɹ ɜ ɫɨɡɞɚɧɢɢ ɧɚɭɱɧɨ-ɬɟɯɧɢɱɟɫɤɨɝɨ ɡɚɞɟɥɚ, ɨɬɤɪɵɜɚɸɳɟɝɨ ɩɨɬɟɧɰɢɚɥɶɧɵɟ ɜɨɡɦɨɠɧɨɫɬɢ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ȽɋɄ ɜ ɬɟɪɚɩɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ. Ȼɟɥɤɢ, ɢɡɦɟɧɟɧɢɟ ɫɨɞɟɪɠɚɧɢɹ ɤɨɬɨɪɵɯ ɨɛɧɚɪɭɠɟɧɨ ɩɪɢ ɪɚɡɜɢɬɢɢ
ɩɚɬɨɥɨɝɢɢ, ɦɨɝɭɬ ɫɨɩɨɫɬɚɜɥɹɬɶɫɹ ɫ ɛɟɥɤɚɦɢ ȽɋɄ ɢ ɨɫɬɟɨɛɥɚɫɬɨɜ, ɚ
ɬɚɤɠɟ ɪɚɫɫɦɚɬɪɢɜɚɬɶɫɹ ɤɚɤ ɛɢɨɦɚɪɤɟɪɵ ɞɥɹ ɞɢɚɝɧɨɫɬɢɤɢ ɩɪɟɞɪɚɫ-
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ɩɨɥɨɠɟɧɧɨɫɬɢ ɤ ɚɬɟɪɨɫɤɥɟɪɨɡɭ, ɱɬɨ ɫɩɨɫɨɛɫɬɜɭɟɬ ɩɟɪɟɯɨɞɭ ɤ ɩɟɪɫɨɧɚɥɢɡɢɪɨɜɚɧɧɨɣ ɦɟɞɢɰɢɧɟ.
ɍɫɨɜɟɪɲɟɧɫɬɜɨɜɚɧɧɵɣ ɦɟɬɨɞ ɩɨɞɝɨɬɨɜɤɢ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɤ ɚɜɬɨɦɚɬɢɡɢɪɨɜɚɧɧɨɦɭ ɩɪɨɬɟɨɦɧɨɦɭ ɚɧɚɥɢɡɭ ɦɨɠɟɬ ɢɫɩɨɥɶɡɨɜɚɬɶɫɹ ɜ
ɤɥɢɧɢɤɚɯ ɫɨɨɬɜɟɬɫɬɜɭɸɳɟɝɨ ɩɪɨɮɢɥɹ.
Ɉɫɧɨɜɧɵɟ ɧɚɭɱɧɵɟ ɪɟɡɭɥɶɬɚɬɵ.
1. ɍɫɨɜɟɪɲɟɧɫɬɜɨɜɚɧɧɵɣ ɦɟɬɨɞ – ɤɨɦɛɢɧɚɰɢɹ 2D ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɫ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɟɦ ɤɥɟɬɨɱɧɵɯ ɨɪɝɚɧɟɥɥ, ɩɨɡɜɨɥɹɸɳɢɣ ɧɟ
ɬɨɥɶɤɨ ɩɪɨɜɟɫɬɢ ɩɪɨɬɟɨɦɧɵɣ ɚɧɚɥɢɡ ɤɥɟɬɨɤ, ɧɨ ɢ ɩɨɥɭɱɢɬɶ ɢɧɮɨɪɦɚɰɢɸ ɨ ɜɧɭɬɪɢɤɥɟɬɨɱɧɨɣ ɥɨɤɚɥɢɡɚɰɢɢ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɯ ɛɟɥɤɨɜ. Ɇɟɬɨɞ ɨɬɥɢɱɚɟɬɫɹ ɜɨɫɩɪɨɢɡɜɨɞɢɦɨɫɬɶɸ ɢ ɜɨɡɦɨɠɧɨɫɬɶɸ ɤɨɥɢɱɟɫɬɜɟɧɧɨɣ ɨɰɟɧɤɢ ɪɟɡɭɥɶɬɚɬɨɜ, ɛɨɥɶɲɢɧɫɬɜɨ ɟɝɨ ɫɬɚɞɢɣ ɚɜɬɨɦɚɬɢɡɢɪɨɜɚɧɨ.
2. ȼ ɷɤɫɩɟɪɢɦɟɧɬɚɯ ɧɚ ɨɫɬɟɨɛɥɚɫɬɚɯ ɩɨɞɬɜɟɪɠɞɟɧɨ, ɱɬɨ ɚɥɝɨɪɢɬɦ
ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ ɨɩɬɢɦɢɡɢɪɨɜɚɧ. Ɉɧ ɦɨɠɟɬ ɩɪɢɦɟɧɹɬɶɫɹ ɞɥɹ ɧɚɛɥɸɞɟɧɢɹ ɡɚ ɞɢɧɚɦɢɤɨɣ ɢɡɦɟɧɟɧɢɹ ɛɟɥɤɨɜ ɜ ɨɬɜɟɬ ɧɚ ɜɧɟɲɧɢɟ ɜɨɡɞɟɣɫɬɜɢɹ, ɜ ɬɨɦ ɱɢɫɥɟ ɧɚ ɜɥɢɹɧɢɟ ɮɚɤɬɨɪɨɜ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ, ɬ.ɟ. ɝɟɦɨɩɨɷɬɢɱɟɫɤɨɣ ɤɥɟɬɨɱɧɨɣ ɧɢɲɢ ɋɄ. ɗɬɨ, ɜ ɫɜɨɸ ɨɱɟɪɟɞɶ, ɞɚɫɬ ɜɨɡɦɨɠɧɨɫɬɶ ɩɪɨɜɨɞɢɬɶ ɷɤɫɩɚɧɫɢɸ ȽɋɄ ɜ ɭɫɥɨɜɢɹɯ in vitro.
3. Ɉɩɢɫɚɧ ɩɪɨɬɟɨɦɧɵɣ ɩɪɨɮɢɥɶ ɆɇɄ ɢ CD34+ȽɋɄ ɫ ɜɵɫɨɤɢɦ
ɪɚɡɪɟɲɟɧɢɟɦ, ɬɨ ɟɫɬɶ ɫɞɟɥɚɧ ɨɱɟɪɟɞɧɨɣ ɲɚɝ ɜ ɩɨɫɬɪɨɟɧɢɢ ɝɥɨɛɚɥɶɧɨɝɨ
ɩɪɨɬɟɨɦɧɨɝɨ ɩɪɨɮɢɥɹ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɤɥɟɬɨɤ ɢ CD34+ ȽɋɄ.
4. ɉɪɨɜɟɞɟɧ ɞɜɭɦɟɪɧɵɣ ɷɥɟɤɬɪɨɮɨɪɟɡ ɛɟɥɤɨɜ ɢɡ ɢɧɬɢɦɵ ɢ ɦɟɞɢɢ
ɚɨɪɬɵ, ɩɨɥɭɱɟɧɵ ɩɪɨɬɟɨɦɧɵɟ ɩɪɨɮɢɥɢ ɪɚɡɥɢɱɧɵɯ ɜɢɞɨɜ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɩɨɪɚɠɟɧɢɣ (ɠɢɪɨɜɚɹ ɢɧɮɢɥɶɬɪɚɰɢɹ, ɠɢɪɨɜɚɹ ɩɨɥɨɫɚ, ɥɢɩɨɮɢɛɪɨɡɧɚɹ ɛɥɹɲɤɚ, ɮɢɛɪɨɡɧɚɹ ɛɥɹɲɤɚ) ɜ ɫɪɚɜɧɟɧɢɢ ɫ ɧɟɩɨɪɚɠɟɧɧɵɦɢ
ɚɬɟɪɨɫɤɥɟɪɨɡɨɦ ɭɱɚɫɬɤɚɦɢ. Ɉɛɧɚɪɭɠɟɧɵ ɛɟɥɤɨɜɵɟ ɩɹɬɧɚ, ɩɪɨɹɜɥɹɸɳɢɟ ɪɚɡɥɢɱɢɹ ɩɪɢ ɫɪɚɜɧɟɧɢɢ ɩɪɨɬɟɨɦɧɵɯ ɩɪɨɮɢɥɟɣ, ɩɨɞɥɟɠɚɳɢɯ ɩɨɞ
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ɧɟɩɨɪɚɠɟɧɧɵɦɢ ɭɱɚɫɬɤɚɦɢ ɢɧɬɢɦɵ ɢ ɦɟɞɢɢ ɢ ɩɨɞ ɥɢɩɨɮɢɛɪɨɡɧɵɦɢ
ɛɥɹɲɤɚɦɢ. ɉɪɟɞɩɪɢɧɹɬɚ ɩɨɩɵɬɤɚ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɷɬɢɯ ɛɟɥɤɨɜ ɫ ɩɨɦɨɳɶɸ MALDI-TOF ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɢ.
5. ɉɨɞɬɜɟɪɠɞɟɧɚ ɪɨɥɶ ɜ ɮɨɪɦɢɪɨɜɚɧɢɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɣ
ɛɥɹɲɤɢ ɬɚɤɢɯ ɧɢɡɤɨɦɨɥɟɤɭɥɹɪɧɵɯ ɛɟɥɤɨɜ, ɤɚɤ ɚɧɧɟɤɫɢɧɵ ɢ ɛɟɥɤɢ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ.
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1. ɉɊɈɌȿɈɆɂɄȺ ɂ ɉɈɌȿɇɐɂȺɅ ɋɌȼɈɅɈȼɕɏ ɄɅȿɌɈɄ
ȾɅə ɌȿɊȺɉɂɂ ȺɌȿɊɈɋɄɅȿɊɈɁȺ
1.1. ɉɪɨɬɟɨɦɢɤɚ ɤɚɤ ɢɧɫɬɪɭɦɟɧɬ ɢɡɭɱɟɧɢɹ ɤɥɟɬɨɤ
ȼ ɩɨɫɥɟɞɧɢɟ ɝɨɞɵ ɬɟɯɧɨɥɨɝɢɢ, ɩɪɢɦɟɧɹɟɦɵɟ ɞɥɹ ɢɫɫɥɟɞɨɜɚɧɢɣ
ɩɪɨɬɟɨɦɚ, ɡɧɚɱɢɬɟɥɶɧɨ ɭɫɨɜɟɪɲɟɧɫɬɜɨɜɚɥɢɫɶ ɛɥɚɝɨɞɚɪɹ ɛɨɥɶɲɟɣ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ ɢ ɫɩɟɰɢɮɢɱɧɨɫɬɢ ɦɟɬɨɞɨɜ, ɢɫɩɨɥɶɡɭɸɳɢɯɫɹ ɜ ɧɢɯ [27].
Ɍɟɦ ɧɟ ɦɟɧɟɟ, ɞɨ ɫɢɯ ɩɨɪ ɫɭɳɟɫɬɜɟɧɧɭɸ ɩɪɨɛɥɟɦɭ ɩɪɟɞɫɬɚɜɥɹɟɬ ɨɬɫɭɬɫɬɜɢɟ ɟɞɢɧɨɣ ɫɯɟɦɵ ɚɧɚɥɢɡɚ, ɤɨɬɨɪɚɹ ɭɩɪɨɳɚɥɚ ɛɵ ɫɪɚɜɧɟɧɢɟ ɞɚɧɧɵɯ, ɩɨɥɭɱɟɧɧɵɯ ɜ ɪɚɡɧɵɯ ɥɚɛɨɪɚɬɨɪɢɹɯ. ȼ ɷɬɨɣ ɫɜɹɡɢ ɜɪɟɦɹ ɨɬ ɜɪɟɦɟɧɢ ɩɪɟɞɩɪɢɧɢɦɚɸɬɫɹ ɩɨɩɵɬɤɢ ɧɟɤɨɟɣ ɫɬɚɧɞɚɪɬɢɡɚɰɢɢ ɩɪɨɬɟɨɦɢɱɟɫɤɢɯ ɩɪɨɰɟɞɭɪ, ɜ ɬɨɦ ɱɢɫɥɟ ɩɨ ɢɧɢɰɢɚɬɢɜɟ ɦɟɠɞɭɧɚɪɨɞɧɵɯ ɧɚɭɱɧɵɯ
ɨɪɝɚɧɢɡɚɰɢɣ (ɜ ɱɚɫɬɧɨɫɬɢ, HUPO) .
Ɇɨɠɧɨ ɭɤɚɡɚɬɶ ɧɚ ɜɧɟɞɪɟɧɢɟ, ɧɚɩɪɢɦɟɪ, ɫɬɚɧɞɚɪɬɧɵɯ ɩɪɨɰɟɞɭɪ
ɤɨɦɩɶɸɬɟɪɧɨɣ ɨɛɪɚɛɨɬɤɢ ɢɡɨɛɪɚɠɟɧɢɣ ɝɟɥɟɣ (ɜ ɮɨɪɦɚɬɟ .tiff ɮɚɣɥɨɜ),
ɱɬɨ ɩɨɡɜɨɥɹɟɬ ɯɪɚɧɢɬɶ ɢɧɮɨɪɦɚɰɢɸ ɫ ɨɞɧɨɬɢɩɧɵɦɢ ɯɚɪɚɤɬɟɪɢɫɬɢɤɚɦɢ. Ɉɞɧɚɤɨ ɦɧɨɝɢɟ ɬɪɭɞɧɨɫɬɢ ɧɚ ɷɬɨɦ ɩɭɬɢ ɨɫɬɚɸɬɫɹ ɧɟɩɪɟɨɞɨɥɟɧɧɵɦɢ ɢ ɞɚɠɟ ɜɨɡɪɚɫɬɚɸɬ ɜ ɫɜɹɡɢ ɫ ɦɨɞɟɪɧɢɡɚɰɢɟɣ ɢ ɞɢɜɟɪɫɢɮɢɤɚɰɢɟɣ
ɢɫɩɨɥɶɡɭɟɦɨɝɨ ɪɚɡɧɵɦɢ ɢɫɫɥɟɞɨɜɚɬɟɥɹɦɢ ɨɛɨɪɭɞɨɜɚɧɢɹ.
Ɍɢɩɢɱɧɚɹ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɶ ɨɩɟɪɚɰɢɣ ɩɪɢ ɢɫɫɥɟɞɨɜɚɧɢɹɯ ɜ
ɩɪɨɬɟɨɦɢɤɟ ɬɚɤɨɜɚ [12]:
− ɨɬɛɨɪ ɨɛɪɚɡɰɚ (ɤɥɟɬɤɢ, ɬɤɚɧɶ, ɛɢɨɥɨɝɢɱɟɫɤɚɹ ɠɢɞɤɨɫɬɶ);
− ɩɪɢɝɨɬɨɜɥɟɧɢɟ ɨɛɪɚɡɰɚ, ɥɢɡɢɫ ɤɥɟɬɨɤ, ɷɤɫɬɪɚɤɰɢɹ ɛɟɥɤɨɜ;
− ɢɡɨɷɥɟɤɬɪɨɮɨɤɭɫɢɪɨɜɤɚ, ɷɥɟɤɬɪɨɮɨɪɟɡ ɜ 1-ɨɦ ɧɚɩɪɚɜɥɟɧɢɢ;
− ɷɥɟɤɬɪɨɮɨɪɟɡ ɜ 2-ɨɦ ɧɚɩɪɚɜɥɟɧɢɢ, ɩɨɥɢɚɤɪɢɥɚɦɢɞɧɵɣ ɝɟɥɶ,
ɞɨɞɟɰɢɥɫɭɥɶɮɚɬ ɧɚɬɪɢɹ;
− ɩɪɨɹɜɥɟɧɢɟ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɧɚ ɝɟɥɟ;
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− ɚɧɚɥɢɡ ɞɜɭɦɟɪɧɨɣ ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦɵ (ɤɨɥɢɱɟɫɬɜɨ ɩɹɬɟɧ, ɢɯ
ɪɚɡɦɟɪ ɢ ɪɚɫɩɨɥɨɠɟɧɢɟ);
− ɜɵɞɟɥɟɧɢɟ ɭɱɚɫɬɤɨɜ ɝɟɥɹ, ɫɨɞɟɪɠɚɳɢɯ ɢɧɞɢɜɢɞɭɚɥɶɧɵɟ ɛɟɥɤɨɜɵɟ ɩɹɬɧɚ;
− ɪɚɫɳɟɩɥɟɧɢɟ ɢɧɞɢɜɢɞɭɚɥɶɧɵɯ ɛɟɥɤɨɜ ɬɪɢɩɫɢɧɨɦ ɩɪɹɦɨ ɜ ɝɟɥɟ;
− ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɱɟɫɤɢɣ ɚɧɚɥɢɡ: ɦɚɫɫ-ɮɢɧɝɟɪɩɪɢɧɬɢɧɝ ɩɟɩɬɢɞɨɜ, ɨɩɪɟɞɟɥɟɧɢɟ ɚɦɢɧɨɤɢɫɥɨɬɧɵɯ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɟɣ ɮɪɚɝɦɟɧɬɨɜ ɢɧɞɢɜɢɞɭɚɥɶɧɵɯ ɛɟɥɤɨɜ, ɢɞɟɧɬɢɮɢɤɚɰɢɹ ɤɚɠɞɨɝɨ ɛɟɥɤɚ ɢ ɢɡɦɟɪɟɧɢɟ ɟɝɨ ɤɨɧɰɟɧɬɪɚɰɢɢ, ɞɨɤɭɦɟɧɬɢɪɨɜɚɧɢɟ, ɨɛɪɚɛɨɬɤɚ ɪɟɡɭɥɶɬɚɬɨɜ.
ɂ, ɧɚɤɨɧɟɰ, ɢɧɬɟɪɩɪɟɬɚɰɢɹ ɩɨɥɭɱɟɧɧɵɯ ɞɚɧɧɵɯ ɫ ɩɨɦɨɳɶɸ ɛɢɨɢɧɮɨɪɦɚɬɢɤɢ, ɚɧɚɥɢɡ ɛɚɡ ɞɚɧɧɵɯ, ɜ ɢɬɨɝɟ – ɩɨɥɭɱɟɧɢɟ ɞɢɮɮɟɪɟɧɰɢɚɥɶɧɨɝɨ ɩɪɨɮɢɥɹ ɛɟɥɤɨɜ.
Ɂɧɚɱɢɬɟɥɶɧɨɦɭ ɩɪɨɝɪɟɫɫɭ ɜ ɨɛɥɚɫɬɢ ɩɪɨɬɟɨɦɢɤɢ ɫɩɨɫɨɛɫɬɜɨɜɚɥɢ
ɭɫɩɟɯɢ ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɱɟɫɤɨɝɨ ɚɧɚɥɢɡɚ ɩɟɩɬɢɞɨɜ [53]. Ɇɚɫɫɫɩɟɤɬɪɨɦɟɬɪɢɹ ɜɤɥɸɱɚɟɬ ɜ ɫɟɛɹ ɬɪɢ ɨɫɧɨɜɧɵɯ ɤɨɦɩɨɧɟɧɬɚ. ȼɨ-ɩɟɪɜɵɯ,
ɜ ɢɨɧɧɨɦ ɢɫɬɨɱɧɢɤɟ ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɚ ɢɡ ɨɛɪɚɡɰɚ ɩɨɥɭɱɚɸɬ ɢɨɧɢɡɢɪɨɜɚɧɧɵɟ ɩɟɩɬɢɞɵ ɢɥɢ ɛɟɥɤɢ. ȼɨ-ɜɬɨɪɵɯ, ɪɚɡɞɟɥɟɧɢɟ ɢɨɧɨɜ ɩɟɩɬɢɞɨɜ
ɢ ɛɟɥɤɨɜ ɩɪɨɢɫɯɨɞɢɬ ɜ ɚɧɚɥɢɡɚɬɨɪɟ ɦɚɫɫ ɧɚ ɨɫɧɨɜɟ ɢɯ ɜɟɥɢɱɢɧɵ ɨɬɧɨɲɟɧɢɹ ɦɚɫɫɵ ɤ ɡɚɪɹɞɭ (m/z). ȼ-ɬɪɟɬɶɢɯ, ɞɟɬɟɤɬɨɪ ɢɨɧɨɜ (ɜɪɟɦɹɩɪɨɥɟɬɧɵɣ ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪ) ɪɟɝɢɫɬɪɢɪɭɟɬ ɨɬɞɟɥɶɧɵɟ ɢɨɧɵ, ɫ ɭɤɚɡɚɧɢɟɦ
ɡɧɚɱɟɧɢɹ m/z ɢɨɧɚ, ɤɨɥɢɱɟɫɬɜɚ ɢɨɧɨɜ ɢ ɜɪɟɦɟɧɢ ɩɪɨɥɟɬɚ ɢɨɧɨɜ ɨɬ ɢɫɬɨɱɧɢɤɚ ɞɨ ɞɟɬɟɤɬɨɪɚ ɢɨɧɨɜ.
ɍɤɚɠɟɦ ɧɚ ɨɫɨɛɟɧɧɨɫɬɢ ɩɪɨɰɟɞɭɪ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ. ȿɝɨ ɷɮɮɟɤɬɢɜɧɨɫɬɶ ɦɨɠɧɨ ɩɨɜɵɫɢɬɶ ɡɚ ɫɱɟɬ ɚɜɬɨɦɚɬɢɡɚɰɢɢ ɪɹɞɚ ɫɬɚɞɢɣ, ɱɬɨ
ɤ ɬɨɦɭ ɠɟ ɨɛɟɫɩɟɱɢɜɚɟɬ ɛɨɥɟɟ ɜɵɫɨɤɭɸ ɩɪɨɢɡɜɨɞɢɬɟɥɶɧɨɫɬɶ ɩɪɨɰɟɫɫɚ,
ɞɚɸɳɭɸ ɜɨɡɦɨɠɧɨɫɬɶ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɬɶ ɞɨ ɧɟɫɤɨɥɶɤɢɯ ɫɨɬɟɧ ɛɟɥɤɨɜ
ɡɚ ɨɞɢɧ ɷɤɫɩɟɪɢɦɟɧɬ. ɇɢɠɟ ɩɪɟɞɫɬɚɜɥɟɧɨ ɤɪɚɬɤɨɟ ɨɩɢɫɚɧɢɟ ɫɬɚɞɢɣ
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ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɨɝɨ ɚɥɝɨɪɢɬɦɚ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ.
ɒɚɝ 1 – ɩɪɢɝɨɬɨɜɥɟɧɢɟ ɨɛɪɚɡɰɚ (ɩɨɥɭɱɟɧɢɟ ɤɥɟɬɨɤ).
Ⱦɥɹ ɛɨɥɶɲɢɧɫɬɜɚ ɩɪɨɬɟɨɦɧɵɯ ɢɫɫɥɟɞɨɜɚɧɢɣ ɢɫɬɨɱɧɢɤ ɞɥɹ ɩɨɥɭɱɟɧɢɹ ɨɛɪɚɡɰɚ ɢɝɪɚɟɬ ɜɚɠɧɟɣɲɭɸ ɪɨɥɶ, ɱɬɨ ɜ ɨɫɨɛɟɧɧɨɫɬɢ ɤɚɫɚɟɬɫɹ
ɭɫɥɨɜɢɣ, ɩɪɟɞɲɟɫɬɜɭɸɳɢɯ ɚɧɚɥɢɡɭ, ɢ ɤɨɥɢɱɟɫɬɜɚ ɨɛɪɚɡɰɚ. ɉɪɢ ɪɚɛɨɬɟ
ɫ ȽɋɄ ɤɨɥɢɱɟɫɬɜɨ ɦɚɬɟɪɢɚɥɚ ɱɚɫɬɨ ɹɜɥɹɟɬɫɹ ɨɝɪɚɧɢɱɟɧɧɵɦ (1–2 ɦɥɧ.
ɤɥɟɬɨɤ ɧɚ ɩɪɨɛɭ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ). ɗɬɨ ɨɡɧɚɱɚɟɬ, ɱɬɨ ɤɚɠɞɚɹ ɩɨɫɥɟɞɭɸɳɚɹ ɫɬɚɞɢɹ ɚɧɚɥɢɡɚ ɞɨɥɠɧɚ ɛɵɬɶ ɜɵɫɨɤɨɷɮɮɟɤɬɢɜɧɨɣ, ɱɬɨɛɵ ɧɟ
ɫɞɟɥɚɬɶ ɩɪɟɞɲɟɫɬɜɭɸɳɭɸ ɪɚɛɨɬɭ ɧɚɩɪɚɫɧɨɣ.
ɒɚɝ 2 – ɥɢɡɢɫ ɤɥɟɬɨɤ (ɩɨɥɭɱɟɧɢɟ ɛɟɥɤɚ).
ȼɵɞɟɥɟɧɢɟ ɛɟɥɤɚ ɢɡ ɤɥɟɬɨɤ – ɧɟ ɦɟɧɟɟ ɜɚɠɧɵɣ ɲɚɝ, ɱɟɦ ɩɪɟɞɵɞɭɳɢɣ. Ɏɨɪɦɚ, ɜ ɤɨɬɨɪɨɣ ɜɵɞɟɥɹɸɬɫɹ ɛɟɥɤɢ, ɨɩɪɟɞɟɥɹɟɬ ɞɚɥɶɧɟɣɲɢɣ
ɯɨɞ ɚɧɚɥɢɡɚ. Ȼɨɥɟɟ ɬɨɝɨ, ɢɫɩɨɥɶɡɨɜɚɧɢɟ ɧɚ ɷɬɨɦ ɷɬɚɩɟ ɫɭɛɤɥɟɬɨɱɧɨɝɨ
ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɹ ɩɨɡɜɨɥɹɟɬ ɭɜɟɥɢɱɢɬɶ ɪɚɡɪɟɲɚɸɳɭɸ ɫɩɨɫɨɛɧɨɫɬɶ
ɦɟɬɨɞɚ ɢ ɟɝɨ ɢɧɮɨɪɦɚɰɢɨɧɧɵɟ ɜɨɡɦɨɠɧɨɫɬɢ.
ɒɚɝ 3 – ɪɚɡɞɟɥɟɧɢɟ ɛɟɥɤɨɜ ɢ ɢɯ ɤɨɥɢɱɟɫɬɜɟɧɧɨɟ ɨɩɪɟɞɟɥɟɧɢɟ.
Ȼɟɥɤɢ, ɜɵɞɟɥɟɧɧɵɟ ɢɡ ɤɥɟɬɨɤ, ɞɨɥɠɧɵ ɛɵɬɶ ɪɚɡɞɟɥɟɧɵ ɞɥɹ ɢɯ
ɞɚɥɶɧɟɣɲɟɣ ɢɞɟɧɬɢɮɢɤɚɰɢɢ. Ⱦɥɹ ɷɬɨɝɨ ɫɭɳɟɫɬɜɭɟɬ ɰɟɥɵɣ ɪɹɞ ɜɨɡɦɨɠɧɨɫɬɟɣ [52], ɩɪɢɦɟɧɹɟɦɵɯ ɜ ɡɚɜɢɫɢɦɨɫɬɢ ɨɬ ɪɹɞɚ ɮɚɤɬɨɪɨɜ. ɍɫɬɨɹɜɲɟɣɫɹ ɚɥɶɬɟɪɧɚɬɢɜɨɣ ɞɥɹ ɩɪɨɬɟɨɦɢɤɢ ɹɜɥɹɟɬɫɹ ɩɪɨɰɟɞɭɪɚ, ɢɡɜɟɫɬɧɚɹ ɤɚɤ ɞɜɭɦɟɪɧɵɣ ɝɟɥɶ-ɷɥɟɤɬɪɨɮɨɪɟɡ (2D).
ɒɚɝ 4 – ɜɢɡɭɚɥɢɡɚɰɢɹ ɢ ɜɵɪɟɡɚɧɢɟ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ.
ɉɨ ɨɤɨɧɱɚɧɢɢ ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɝɟɥɶ ɨɩɭɫɤɚɸɬ ɜ ɛɭɮɟɪ ɞɥɹ ɩɟɪɟɧɨɫɚ. ɉɨɫɥɟ ɪɚɡɞɟɥɟɧɢɹ ɞɜɭɦɟɪɧɵɦ ɷɥɟɤɬɪɨɮɨɪɟɡɨɦ ɢ ɨɤɪɚɲɢɜɚɧɢɹ Ʉɭɦɚɫɫɢ R350, ɤɭɫɨɱɤɢ ɝɟɥɹ ɞɢɚɦɟɬɪɨɦ 1–1,5 ɦɦ, ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɟ ɛɟɥɤɨɜɵɦ ɩɹɬɧɚɦ, ɜɵɪɟɡɚɸɬ.
Ɉɤɪɚɲɢɜɚɧɢɟ ɛɟɥɤɨɜɨɝɨ ɝɟɥɹ – ɲɚɝ ɤ ɜɵɪɟɡɚɧɢɸ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ.
Ɉɤɪɚɲɢɜɚɧɢɟ ɛɟɥɤɚ ɩɨɡɜɨɥɹɟɬ ɨɛɧɚɪɭɠɢɬɶ ɢ ɧɢɡɤɨɤɨɧɰɟɧɬɪɢɪɨɜɚɧ11
ɧɵɟ ɛɟɥɤɢ, ɧɨ ɩɪɢ ɷɬɨɦ ɧɟ ɬɪɟɛɭɟɬɫɹ ɛɨɥɶɲɨɣ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ, ɬɚɤ
ɤɚɤ ɥɢɦɢɬɢɪɭɸɳɢɦ ɮɚɤɬɨɪɨɦ ɹɜɥɹɟɬɫɹ ɜɟɥɢɱɢɧɚ ɤɨɧɰɟɧɬɪɚɰɢɢ, ɧɟɨɛɯɨɞɢɦɚɹ ɞɥɹ ɩɨɫɥɟɞɭɸɳɟɝɨ ɩɨɥɭɱɟɧɢɹ ɛɟɥɤɨɜ ɜ ɤɨɥɢɱɟɫɬɜɟ, ɬɪɟɛɭɟɦɨɦ ɞɥɹ ɢɯ ɢɞɟɧɬɢɮɢɤɚɰɢɢ. Ɉɛɨɪɭɞɨɜɚɧɢɟ, ɢɫɩɨɥɶɡɭɟɦɨɟ ɞɥɹ ɜɢɡɭɚɥɢɡɚɰɢɢ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ, ɧɟ ɞɨɥɠɧɨ ɜɥɢɹɬɶ ɧɚ ɫɩɨɫɨɛɧɨɫɬɶ ɢɫɫɥɟɞɨɜɚɬɟɥɹ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɬɶ ɢ ɜɵɞɟɥɹɬɶ ɩɹɬɧɚ ɢɧɞɢɜɢɞɭɚɥɶɧɵɯ ɛɟɥɤɨɜ,
ɱɬɨ ɱɚɫɬɨ ɜɫɬɪɟɱɚɟɬɫɹ ɜ ɨɛɪɚɡɰɚɯ ɫ ɧɢɡɤɢɦ ɪɚɡɪɟɲɟɧɢɟɦ. ȼ ɢɞɟɚɥɟ,
ɩɪɨɰɟɞɭɪɚ ɜɵɪɟɡɚɧɢɹ ɛɟɥɤɨɜ ɞɨɥɠɧɚ ɛɵɬɶ ɚɜɬɨɦɚɬɢɡɢɪɨɜɚɧɚ ɜ ɢɧɬɟɪɟɫɚɯ ɬɨɱɧɨɫɬɢ ɢ ɷɮɮɟɤɬɢɜɧɨɫɬɢ ɚɧɚɥɢɡɚ.
ɒɚɝ 5 – ɩɟɪɟɜɚɪɢɜɚɧɢɟ ɢ ɢɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ.
ɉɟɪɟɜɚɪɢɜɚɧɢɟ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɩɨɞ ɞɟɣɫɬɜɢɟɦ ɬɪɢɩɫɢɧɚ, ɤɚɤ ɩɪɚɜɢɥɨ, ɦɧɨɝɨɤɪɚɬɧɚɹ ɩɪɨɰɟɞɭɪɚ, ɤɨɬɨɪɭɸ ɩɪɟɞɩɨɱɬɢɬɟɥɶɧɨ ɚɜɬɨɦɚɬɢɡɢɪɨɜɚɬɶ ɞɥɹ ɫɧɢɠɟɧɢɹ ɜɚɪɢɚɛɟɥɶɧɨɫɬɢ ɨɬ ɩɪɨɛɵ ɤ ɩɪɨɛɟ ɢ ɭɫɬɪɚɧɟɧɢɹ
ɞɪɭɝɢɯ ɨɲɢɛɨɤ. Ɍɚɤɠɟ ɩɪɟɞɩɨɱɬɢɬɟɥɶɧɚ ɚɜɬɨɦɚɬɢɡɚɰɢɹ ɢ ɞɥɹ ɩɪɨɰɟɞɭɪɵ ɧɚɧɟɫɟɧɢɹ ɩɟɪɟɜɚɪɟɧɧɨɝɨ ɨɛɪɚɡɰɚ ɧɚ ɩɥɚɬɵ ɞɥɹ MALDIɢɞɟɧɬɢɮɢɤɚɰɢɢ. ɉɪɨɞɭɤɬɵ ɝɢɞɪɨɥɢɡɚ ɫɦɟɲɢɜɚɸɬ ɩɪɹɦɨ ɧɚ ɩɥɚɫɬɢɧɤɟ
ɞɥɹ
ɦɚɫɫ-ɫɩɟɤɬɪɨɫɤɨɩɢɢ
ɫ
ɦɚɬɪɢɰɟɣ
(ɚɥɶɮɚ-ɰɢɚɧɨ-4-ɝɢɞɪɨɨɤɫɢ-
ɤɨɪɢɱɧɚɹ ɤɢɫɥɨɬɚ, ɧɚɫɵɳɟɧɧɵɣ ɪɚɫɬɜɨɪ ɜ ɚɰɟɬɨɧɟ). ɉɪɢɫɜɨɟɧɢɟ ID
(ɢɞɟɧɬɢɮɢɤɚɰɢɨɧɧɨɝɨ ɧɨɦɟɪɚ) ɛɟɥɤɭ ɞɚɧɧɨɝɨ ɨɛɪɚɡɰɚ – ɩɨɫɥɟɞɧɢɣ ɲɚɝ
ɚɧɚɥɢɡɚ, ɫ ɭɱɟɬɨɦ ɭɫɬɚɧɨɜɥɟɧɧɨɝɨ ɤɪɢɬɟɪɢɹ ɧɚɞɟɠɧɨɫɬɢ ɞɥɹ ɜɫɟɯ ɩɪɨɰɟɞɭɪ. ȼ ɷɬɨɦ ɫɥɭɱɚɟ ɨɛɟɫɩɟɱɢɜɚɟɬɫɹ ɜɨɫɩɪɨɢɡɜɨɞɢɦɨɫɬɶ ɪɟɡɭɥɶɬɚɬɨɜ
ɤɚɤ ɜɧɭɬɪɢ-, ɬɚɤ ɢ ɦɟɠɥɚɛɨɪɚɬɨɪɧɵɯ ɷɤɫɩɟɪɢɦɟɧɬɨɜ.
ɇɚɥɢɱɢɟ ɜ ɨɩɢɫɚɧɧɨɦ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɨɦ ɚɥɝɨɪɢɬɦɟ ɱɟɬɤɨ ɨɱɟɪɱɟɧɧɵɯ ɫɬɚɞɢɣ (ɲɚɝɨɜ) ɩɨɡɜɨɥɹɟɬ ɩɪɢ ɧɟɨɛɯɨɞɢɦɨɫɬɢ ɩɪɟɪɜɚɬɶ ɜɵɩɨɥɧɟɧɢɟ ɩɪɨɬɨɤɨɥɚ ɧɚ ɩɟɪɢɨɞ, ɩɪɟɜɵɲɚɸɳɢɣ ɞɚɠɟ 24 ɱɚɫɚ, ɛɟɡ ɭɳɟɪɛɚ ɞɥɹ
ɰɟɥɨɫɬɧɨɫɬɢ ɩɪɨɛɵ. Ɍɚɤɢɦɢ ɬɨɱɤɚɦɢ ɩɪɟɪɵɜɚɧɢɹ ɢ ɯɪɚɧɟɧɢɹ ɦɨɝɭɬ ɛɵɬɶ
ɫɥɟɞɭɸɳɢɟ.
1. ɏɪɚɧɟɧɢɟ IPG-ɫɬɪɢɩɨɜ ɩɨɫɥɟ ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɜ ɩɟɪɜɨɦ ɧɚɩɪɚɜ12
ɥɟɧɢɢ. IPG-ɫɬɪɢɩɵ ɞɨɥɠɧɵ ɛɵɬɶ ɡɚɳɢɳɟɧɵ ɨɬ ɮɢɡɢɱɟɫɤɨɝɨ ɩɨɜɪɟɠɞɟɧɢɹ (ɧɚɩɪɢɦɟɪ, ɰɟɥɥɨɮɚɧɨɦ) ɢ ɯɪɚɧɢɬɶɫɹ ɩɪɢ ɬɟɦɩɟɪɚɬɭɪɟ –20°C.
Ɂɚɦɨɪɚɠɢɜɚɧɢɟ ɨɛɪɚɡɰɚ ɩɪɟɞɨɬɜɪɚɳɚɟɬ ɞɢɮɮɭɡɢɸ ɢɡɨɷɥɟɤɬɪɢɱɟɫɤɢ
ɮɨɤɭɫɢɪɨɜɚɧɧɵɯ ɛɟɥɤɨɜ ɢɡ ɫɬɪɢɩɨɜ. Ɉɬɬɚɢɜɚɧɢɟ ɫɥɟɞɭɟɬ ɩɪɨɢɡɜɨɞɢɬɶ ɩɪɢ ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ. Ɏɚɤɬɢɱɟɫɤɢ, ɷɬɚ ɬɨɱɤɚ ɩɪɟɪɵɜɚɧɢɹ
ɹɜɥɹɟɬɫɹ ɩɟɪɜɨɣ, ɤɨɝɞɚ ɩɪɨɛɚ ɦɨɠɟɬ ɯɪɚɧɢɬɶɫɹ ɛɟɡ ɧɚɪɭɲɟɧɢɹ ɫɜɨɟɣ
ɰɟɥɨɫɬɧɨɫɬɢ, ɬɟɦ ɛɨɥɟɟ, ɱɬɨ ɩɪɨɞɨɥɠɢɬɟɥɶɧɨɫɬɶ ɨɩɵɬɚ ɨɬ ɫɛɨɪɚ ɤɥɟɬɨɤ ɞɨ ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɜ ɩɟɪɜɨɦ ɧɚɩɪɚɜɥɟɧɢɢ ɫɨɫɬɚɜɥɹɟɬ ɩɪɢɦɟɪɧɨ
ɨɞɢɧ ɪɚɛɨɱɢɣ ɞɟɧɶ.
2. MALDI-ɩɥɚɬɵ, ɫɨɞɟɪɠɚɳɢɟ ɦɚɬɪɢɰɭ, ɫɦɟɲɚɧɧɭɸ ɫ ɩɟɪɟɜɚɪɟɧɧɵɦ ɛɟɥɤɨɦ, ɦɨɝɭɬ ɯɪɚɧɢɬɶɫɹ ɩɪɢ ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ, ɛɭɞɭɱɢ
ɝɟɪɦɟɬɢɱɧɨ ɭɤɭɩɨɪɟɧɧɵɦɢ. Ɍɚɤɨɣ ɨɛɪɚɡɟɰ ɦɨɠɟɬ ɯɪɚɧɢɬɶɫɹ ɞɨɫɬɚɬɨɱɧɨ ɞɨɥɝɨ ɩɟɪɟɞ MALDI-ɚɧɚɥɢɡɨɦ. ɗɬɨɬ ɦɨɦɟɧɬ ɜɪɟɦɟɧɢ (ɩɨɫɥɟ ɨɬɛɨɪɚ
ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɢ ɢɯ ɩɟɪɟɜɚɪɢɜɚɧɢɹ) ɢɞɟɚɥɟɧ ɞɥɹ ɨɫɬɚɧɨɜɤɢ ɩɟɪɟɞ
MALDI-ɢɞɟɧɬɢɮɢɤɚɰɢɟɣ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɜɟɫɶ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɣ
ɚɥɝɨɪɢɬɦ ɭɞɨɛɧɨ ɪɚɡɞɟɥɢɬɶ ɧɚ ɞɜɟ ɪɚɛɨɱɢɟ ɮɚɡɵ ɛɟɡ ɭɳɟɪɛɚ ɞɥɹ ɰɟɥɨɫɬɧɨɫɬɢ ɢɡɭɱɚɟɦɨɝɨ ɨɛɪɚɡɰɚ.
Ɇɟɬɨɞɵ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ ɧɚɰɟɥɟɧɵ ɧɚ ɩɪɨɪɚɛɨɬɤɭ ɞɜɭɯ ɜɚɪɢɚɧɬɨɜ ɫɨɜɟɪɲɟɧɫɬɜɨɜɚɧɢɹ ɫɤɪɢɧɢɧɝɚ, ɞɢɚɝɧɨɫɬɢɤɢ ɢ ɦɨɧɢɬɨɪɢɧɝɚ
ɪɚɡɥɢɱɧɵɯ ɡɚɛɨɥɟɜɚɧɢɣ. ɉɟɪɜɵɣ ɩɪɟɞɫɬɚɜɥɹɟɬ ɫɨɛɨɣ ɢɞɟɚɥɶɧɭɸ ɫɯɟɦɭ
ɪɟɲɟɧɢɹ ɩɪɨɛɥɟɦɵ ɱɟɪɟɡ ɨɬɤɪɵɬɢɟ ɬ.ɧ. «ɛɢɨɦɚɪɤɟɪɨɜ» – ɬɚɤɢɯ ɜɟɳɟɫɬɜ, ɤɨɬɨɪɵɟ ɩɨɹɜɥɹɸɬɫɹ ɜ ɬɤɚɧɹɯ ɢ ɛɢɨɥɨɝɢɱɟɫɤɢɯ ɠɢɞɤɨɫɬɹɯ ɨɪɝɚɧɢɡɦɚ ɬɨɥɶɤɨ ɩɪɢ ɫɬɪɨɝɨ ɨɩɪɟɞɟɥɟɧɧɵɯ ɩɚɬɨɥɨɝɢɱɟɫɤɢɯ ɩɪɨɰɟɫɫɚɯ,
ɥɟɝɤɨ ɞɟɬɟɤɬɢɪɭɸɬɫɹ ɫɨɜɪɟɦɟɧɧɵɦɢ ɛɢɨɯɢɦɢɱɟɫɤɢɦɢ ɩɪɢɥɨɠɟɧɢɹɦɢ
ɢ ɫ ɦɚɤɫɢɦɚɥɶɧɨ ɜɵɫɨɤɨɣ ɞɨɥɟɣ ɜɟɪɨɹɬɧɨɫɬɢ ɫɜɢɞɟɬɟɥɶɫɬɜɭɸɬ ɨ ɤɨɧɤɪɟɬɧɨɦ ɡɚɛɨɥɟɜɚɧɢɢ ɩɪɢ ɨɛɧɚɪɭɠɟɧɢɢ ɭ ɤɨɧɤɪɟɬɧɨɝɨ ɩɚɰɢɟɧɬɚ. Ⱦɟɬɟɤɰɢɹ ɬɚɤɨɝɨ ɛɢɨɦɚɪɤɟɪɚ ɜɨ ɜɡɹɬɵɯ ɞɥɹ ɚɧɚɥɢɡɚ ɛɢɨɥɨɝɢɱɟɫɤɢɯ ɨɛɪɚɡɰɚɯ ɦɨɠɟɬ ɥɟɱɶ ɜ ɨɫɧɨɜɭ ɞɢɚɝɧɨɫɬɢɱɟɫɤɨɝɨ ɬɟɫɬɚ, ɨɛɥɚɞɚɸɳɟɝɨ ɫɚ13
ɦɵɦ ɩɪɨɝɪɟɫɫɢɜɧɵɦ ɫɨɱɟɬɚɧɢɟɦ ɨɩɟɪɚɰɢɨɧɧɵɯ ɯɚɪɚɤɬɟɪɢɫɬɢɤ – ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ, ɫɩɟɰɢɮɢɱɧɨɫɬɢ, ɬɨɱɧɨɫɬɢ, ɜɨɫɩɪɨɢɡɜɨɞɢɦɨɫɬɢ ɪɟɡɭɥɶɬɚɬɨɜ ɢ ɞɪ. [42].
Ɉɞɧɚɤɨ ɜ ɪɟɚɥɶɧɨɫɬɢ «ɨɬɪɚɛɨɬɚɬɶ» ɢɞɟɚɥɶɧɵɣ ɛɢɨɦɚɪɤɟɪ ɞɥɹ ɤɚɠɞɨɣ ɧɨɡɨɥɨɝɢɱɟɫɤɨɣ ɟɞɢɧɢɰɵ ɩɨɤɚ ɧɟ ɭɞɚɟɬɫɹ. ɑɚɳɟ ɝɨɜɨɪɹɬ ɨ «ɩɪɨɬɟɨɦɧɵɯ ɩɪɨɮɚɣɥɚɯ» – ɰɟɥɵɯ ɫɩɟɤɬɪɚɯ ɞɨɜɨɥɶɧɨ ɫɩɟɰɢɮɢɱɧɵɯ ɛɟɥɤɨɜ ɢ
ɩɟɩɬɢɞɨɜ, ɤɨɬɨɪɵɟ ɯɚɪɚɤɬɟɪɧɵ ɞɥɹ ɬɟɯ ɢɥɢ ɢɧɵɯ ɩɚɬɨɥɨɝɢɱɟɫɤɢɯ ɫɨɫɬɨɹɧɢɣ ɫ ɦɢɧɢɦɚɥɶɧɨɣ ɢɧɞɢɜɢɞɭɚɥɶɧɨ-ɬɢɩɨɥɨɝɢɱɟɫɤɨɣ ɪɚɡɧɢɰɟɣ. ɋɩɟɰɢɮɢɱɧɨɫɬɶ ɩɪɨɮɚɣɥɚ ɞɥɹ ɤɨɧɤɪɟɬɧɨɝɨ ɡɚɛɨɥɟɜɚɧɢɹ (ɢɯ ɝɪɭɩɩɵ) ɨɰɟɧɢɜɚɸɬ ɧɚ ɨɫɧɨɜɚɧɢɢ ɩɚɬɨɥɨɝɢɱɟɫɤɢɯ ɢɡɦɟɧɟɧɢɣ ɫɨɞɟɪɠɚɧɢɹ ɜ ɨɛɪɚɡɰɟ
ɩɪɨɬɟɢɧɨɜ ɜ ɨɩɪɟɞɟɥɟɧɧɵɯ ɞɢɚɩɚɡɨɧɚɯ ɦɚɫɫ, ɩɪɟɨɛɥɚɞɚɧɢɹ ɥɢɛɨ ɧɟɞɨɫɬɚɬɨɱɧɨɫɬɢ ɩɨɥɢɩɟɩɬɢɞɨɜ ɨɩɪɟɞɟɥɟɧɧɵɯ ɝɪɭɩɩ, ɦɧɨɠɟɫɬɜɟɧɧɨɫɬɢ ɚɧɨɦɚɥɶɧɵɯ ɢɡɨɮɨɪɦ/ ɬɪɚɧɫɮɨɪɦɚɰɢɣ ɫɯɨɞɧɨɝɨ ɨɛɪɚɡɚ ɞɥɹ ɪɚɡɧɵɯ ɛɟɥɤɨɜ.
ɍɠɟ ɫɨɡɞɚɧɵ ɛɚɡɵ ɞɚɧɧɵɯ ɩɨ ɫɨɬɧɹɦ ɛɟɥɤɨɜ ɩɪɨɬɟɨɦɚ ɦɢɨɤɚɪɞɚ,
ɭɪɨɜɧɢ ɤɨɬɨɪɵɯ ɢɡɦɟɧɹɸɬɫɹ ɩɪɢ ɯɪɨɧɢɱɟɫɤɢɯ ɢ ɨɫɬɪɵɯ ɫɟɪɞɟɱɧɨɫɨɫɭɞɢɫɬɵɯ ɩɚɬɨɥɨɝɢɹɯ [17]. Ɉɛɧɚɪɭɠɟɧɨ, ɱɬɨ ɩɪɢ ɬɚɤɢɯ ɩɚɬɨɥɨɝɢɹɯ
ɜɨɡɪɚɫɬɚɸɬ ɤɨɧɰɟɧɬɪɚɰɢɢ ɬ.ɧ. ɛɟɥɤɨɜ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ (heat-shock proteins – HSP), ɛɟɥɤɨɜ ɦɢɬɨɯɨɧɞɪɢɣ, ɚ ɬɚɤɠɟ ɛɟɥɤɨɜ, ɜɨɜɥɟɱɟɧɧɵɯ ɜ ɝɟɧɟɪɢɪɨɜɚɧɢɟ ɷɧɟɪɝɢɢ.
1.2. ɋɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ, ɚɬɟɪɨɫɤɥɟɪɨɡ ɢ ɩɪɨɬɟɨɦɢɤɚ
ɋɟɪɞɟɱɧɨ-ɫɨɫɭɞɢɫɬɚɹ ɫɢɫɬɟɦɚ ɫɨɫɬɨɢɬ (ɋɋɋ) ɢɡ ɛɨɥɶɲɨɝɨ ɤɨɥɢɱɟɫɬɜɚ ɫɩɟɰɢɚɥɢɡɢɪɭɸɳɢɯɫɹ ɤɥɟɬɨɱɧɵɯ ɬɢɩɨɜ, ɜɤɥɸɱɚɹ ɦɢɨɰɢɬɵ,
ɮɢɛɪɨɛɥɚɫɬɵ, ɨɫɬɟɨɛɥɚɫɬɵ, ɧɟɣɪɨɧɵ, ɷɧɞɨɬɟɥɢɚɥɶɧɵɟ ɢ ɝɥɚɞɤɨɦɵɲɟɱɧɵɟ ɤɥɟɬɤɢ, ɚ ɬɚɤɠɟ ɫɬɜɨɥɨɜɵɟ ɢ ɩɪɨɝɟɧɢɬɨɪɧɵɟ ɤɥɟɬɤɢ. Ʉ ɫɨɠɚɥɟɧɢɸ, ɩɪɨɬɟɨɦ ɛɨɥɶɲɢɧɫɬɜɚ ɷɬɢɯ ɤɥɟɬɨɤ ɤ ɧɚɫɬɨɹɳɟɦɭ ɜɪɟɦɟɧɢ ɢɡɭɱɟɧ ɧɟɞɨɫɬɚɬɨɱɧɨ ɢ ɦɚɥɨɢɡɜɟɫɬɧɨɣ ɨɫɬɚɟɬɫɹ ɟɝɨ ɫɜɹɡɶ ɫ ɩɚɬɨɥɨɝɢɱɟɫɤɢɦɢ ɫɨɫɬɨɹɧɢɹɦɢ ɫɚɦɨɣ ɫɢɫɬɟɦɵ.
14
Ɍɟɦ ɧɟ ɦɟɧɟɟ, ɧɟɞɚɜɧɢɟ ɤɥɢɧɢɱɟɫɤɢɟ ɢɫɫɥɟɞɨɜɚɧɢɹ ɩɨɤɚɡɵɜɚɸɬ,
ɱɬɨ ɧɟɞɢɮɮɟɪɟɧɰɢɪɨɜɚɧɧɵɟ ɤɥɟɬɤɢ, ɰɢɪɤɭɥɢɪɭɸɳɢɟ ɜ ɤɪɨɜɨɬɨɤɟ,
ɢɦɟɸɬ ɨɝɪɨɦɧɵɣ ɩɨɬɟɧɰɢɚɥ ɞɥɹ ɪɟɝɟɧɟɪɚɰɢɢ ɫɨɫɭɞɢɫɬɨɣ ɬɤɚɧɢ [76].
Ɉɧɢ ɩɚɬɪɭɥɢɪɭɸɬ ɨɪɝɚɧɢɡɦ ɢ ɦɢɝɪɢɪɭɸɬ ɤ ɦɟɫɬɭ, ɝɞɟ ɨɛɧɚɪɭɠɢɜɚɸɬ
ɩɨɜɪɟɠɞɟɧɢɟ ɫɨɫɭɞɚ. Ɉɞɧɚɤɨ, ɧɟɩɨɫɪɟɞɫɬɜɟɧɧɨ ɮɭɧɤɰɢɨɧɚɥɶɧɨɟ ɢɯ
ɞɟɣɫɬɜɢɟ ɡɚɜɢɫɢɬ ɨɬ ɦɧɨɝɢɯ ɮɚɤɬɨɪɨɜ, ɬɚɤɢɯ, ɤɚɤ ɫɩɨɫɨɛɧɨɫɬɶ ɩɪɢɤɪɟɩɥɹɬɶɫɹ ɤ ɷɧɞɨɬɟɥɢɸ, ɦɢɝɪɢɪɨɜɚɬɶ, ɪɚɡɦɧɨɠɚɬɶɫɹ, ɩɨɞɞɟɪɠɢɜɚɬɶ ɫɨɛɫɬɜɟɧɧɭɸ ɠɢɡɧɟɫɩɨɫɨɛɧɨɫɬɶ.
ɂɡɜɟɫɬɧɨ, ɱɬɨ ɩɪɢ ɞɢɚɛɟɬɟ ɭɯɭɞɲɚɟɬɫɹ ɮɭɧɤɰɢɨɧɢɪɨɜɚɧɢɟ ɬɚɤ ɧɚɡɵɜɚɟɦɵɯ ɤɥɟɬɨɤ-ɩɪɟɞɲɟɫɬɜɟɧɧɢɤɨɜ ɷɧɞɨɬɟɥɢɹ ɢ ɩɨɞɚɜɥɹɟɬɫɹ ɦɢɝɪɚɰɢɹ ɦɨɧɨɰɢɬɨɜ, ɢɦɟɸɳɚɹ ɜɚɠɧɨɟ ɡɧɚɱɟɧɢɹ ɞɥɹ ɜɨɫɫɬɚɧɨɜɥɟɧɢɹ ɫɨɫɭɞɨɜ ɢ ɨɛɪɚɡɨɜɚɧɢɹ ɩɚɪɚɥɥɟɥɶɧɵɯ ɩɟɪɢɮɟɪɢɱɟɫɤɢɯ ɫɨɫɭɞɨɜ ɜ ɫɥɭɱɚɟ
ɩɨɜɪɟɠɞɟɧɢɹ [97].
Ⱥɬɟɪɨɫɤɥɟɪɨɡ ɹɜɥɹɟɬɫɹ ɨɞɧɨɣ ɢɡ ɧɚɢɛɨɥɟɟ ɜɚɠɧɵɯ ɦɟɞɢɤɨɫɨɰɢɚɥɶɧɵɯ ɩɪɨɛɥɟɦ, ɢ ɟɝɨ ɤɥɢɧɢɱɟɫɤɢɟ ɩɪɨɹɜɥɟɧɢɹ ɡɚɧɢɦɚɸɬ ɜɟɞɭɳɟɟ ɦɟɫɬɨ ɜ ɫɬɪɭɤɬɭɪɟ ɡɚɛɨɥɟɜɚɟɦɨɫɬɢ ɢ ɫɦɟɪɬɧɨɫɬɢ. Ɍɳɚɬɟɥɶɧɵɣ
ɚɧɚɥɢɡ ɛɟɥɤɨɜ ɢɡ ɩɨɪɚɠɟɧɧɨɣ ɚɬɟɪɨɫɤɥɟɪɨɡɨɦ ɬɤɚɧɢ ɚɪɬɟɪɢɣ ɦɨɝ ɛɵ
ɨɛɧɚɪɭɠɢɬɶ ɜɢɞɵ ɛɟɥɤɨɜ, ɤɨɬɨɪɵɟ ɭɱɚɫɬɜɭɸɬ ɜ ɫɨɫɭɞɢɫɬɨɦ ɪɟɦɨɞɟɥɢɪɨɜɚɧɢɢ ɢ ɚɬɟɪɨɝɟɧɟɡɟ. ɂɞɟɧɬɢɮɢɤɚɰɢɹ ɱɟɥɨɜɟɱɟɫɤɨɝɨ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ ɩɪɨɬɟɨɦɚ – ɮɭɧɞɚɦɟɧɬ ɞɥɹ ɞɚɥɶɧɟɣɲɢɯ ɢɫɫɥɟɞɨɜɚɧɢɣ, ɨɫɧɨɜɚ
ɞɥɹ ɩɨɫɬɪɨɟɧɢɹ ɢ ɩɪɨɜɟɪɤɢ ɧɨɜɵɯ ɝɢɩɨɬɟɡ. Ɉɱɟɜɢɞɧɨ, ɱɬɨ ɜɵɹɜɥɟɧɢɟ
ɮɭɧɤɰɢɨɧɚɥɶɧɨɣ ɫɜɹɡɢ ɦɟɠɞɭ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɦɢ ɩɨɪɚɠɟɧɢɹɦɢ ɢ
ɩɪɨɬɟɨɦɧɵɦ ɩɪɨɮɢɥɟɦ ɢɧɬɢɦɵ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ ɢɦɟɟɬ ɢɫɤɥɸɱɢɬɟɥɶɧɨɟ ɡɧɚɱɟɧɢɟ ɞɥɹ ɩɨɧɢɦɚɧɢɹ ɢɧɢɰɢɢɪɭɸɳɢɯ ɩɪɢɱɢɧ ɜɨɡɧɢɤɧɨɜɟɧɢɹ
ɚɬɟɪɨɫɤɥɟɪɨɡɚ. Ɉɞɧɚɤɨ ɞɨ ɧɚɫɬɨɹɳɟɝɨ ɜɪɟɦɟɧɢ ɥɢɲɶ ɜ ɨɱɟɧɶ ɧɟɛɨɥɶɲɨɦ ɤɨɥɢɱɟɫɬɜɟ ɪɚɛɨɬ ɛɵɥɢ ɢɫɫɥɟɞɨɜɚɧɵ ɛɟɥɤɢ, ɜɵɞɟɥɟɧɧɵɟ ɢɡ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɛɥɹɲɟɤ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ [29, 31, 56]. Ɉɫɨɛɵɣ ɢɧɬɟɪɟɫ ɩɪɢ ɩɪɨɜɟɞɟɧɢɢ ɞɚɥɶɧɟɣɲɢɯ ɢɫɫɥɟɞɨɜɚɧɢɣ ɩɪɟɞɫɬɚɜɥɹɸɬ ɩɪɨɬɟ15
ɨɦɧɵɟ ɩɪɨɮɢɥɢ ɢɧɬɢɦɵ ɢ ɦɟɞɢɢ ɚɪɬɟɪɢɣ ɩɪɢ ɪɚɡɧɵɯ ɫɬɚɞɢɹɯ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ ɩɨɪɚɠɟɧɢɹ.
ɉɨɹɜɥɹɸɬɫɹ ɢ ɧɨɜɵɟ ɞɚɧɧɵɟ ɨɛ ɭɱɚɫɬɢɢ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ (ɋɄ)
ɤɚɤ ɝɟɦɨɩɨɷɬɢɱɟɫɤɨɣ, ɬɚɤ ɢ ɫɬɪɨɦɚɥɶɧɨɣ ɥɢɧɢɣ ɞɢɮɮɟɪɟɧɰɢɪɨɜɤɢ, ɜ
ɚɬɟɪɨɝɟɧɟɡɟ [7, 51, 58, 62]. Ɍɚɤɢɟ ɞɚɧɧɵɟ ɩɨɡɜɨɥɢɥɢ ɩɪɟɞɩɨɥɨɠɢɬɶ, ɱɬɨ
ɜɚɠɧɵɦ ɦɨɦɟɧɬɨɦ ɜ ɪɚɡɜɢɬɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɹɜɥɹɟɬɫɹ ɩɪɨɧɢɤɧɨɜɟɧɢɟ
ɤɨɥɨɧɢɟɨɛɪɚɡɭɸɳɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɝɟɦɨɩɨɷɬɢɱɟɫɤɨɣ ɢ ɫɬɪɨɦɚɥɶɧɨɣ ɥɢɧɢɣ ɞɢɮɮɟɪɟɧɰɢɪɨɜɤɢ ɜ ɢɧɬɢɦɭ ɜ ɦɟɫɬɚɯ ɤɨɧɰɟɧɬɪɚɰɢɢ ɥɢɩɢɞɨɜ. Ɉɛɧɚɪɭɠɟɧɢɟ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɢ ɫɬɪɨɦɚɥɶɧɵɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤɩɪɟɞɲɟɫɬɜɟɧɧɢɤɨɜ ɜ ɢɧɬɢɦɟ ɚɬɟɪɨɦɚɬɨɡɧɨɣ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ ɫɜɢɞɟɬɟɥɶɫɬɜɭɟɬ ɨ ɰɢɪɤɭɥɹɰɢɢ ɷɬɢɯ ɤɥɟɬɨɤ ɜ ɤɪɨɜɨɬɨɤɟ [5, 6].
Ɇɟɬɨɞɚɦɢ ɤɥɨɧɚɥɶɧɨɝɨ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ ɢɧɬɢɦɚɥɶɧɵɯ ɤɥɟɬɨɤ ɢɡ
ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢ ɢɡɦɟɧɟɧɧɵɯ ɭɱɚɫɬɤɨɜ ɚɪɬɟɪɢɣ ɛɵɥɢ ɨɛɧɚɪɭɠɟɧɵ
ɫɬɜɨɥɨɜɵɟ ɤɨɥɨɧɢɟɨɛɪɚɡɭɸɳɢɟ ɤɥɟɬɤɢ, ɤɨɬɨɪɵɟ ɮɨɪɦɢɪɨɜɚɥɢ ɜ ɬɟɫɬɫɢɫɬɟɦɚɯ ɤɚɤ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɟ, ɬɚɤ ɢ ɫɬɪɨɦɚɥɶɧɵɟ ɤɨɥɨɧɢɢ. Ʉɥɟɬɤɢ ɜ
ɫɮɨɪɦɢɪɨɜɚɧɧɵɯ ɫɬɪɨɦɚɥɶɧɵɯ ɤɨɥɨɧɢɹɯ ɫɢɧɬɟɡɢɪɨɜɚɥɢ ɤɨɥɥɚɝɟɧɨɜɵɣ
ɮɢɛɪɢɥɥɹɪɧɵɣ ɢ ɨɫɬɟɨɢɞɧɵɣ ɦɚɬɪɢɤɫɵ [72]. Ʉɭɥɶɬɢɜɢɪɨɜɚɧɢɟ ɤɥɟɬɨɤ
ɦɨɧɨɧɭɤɥɟɚɪɧɨɣ ɮɪɚɤɰɢɢ ɩɟɪɢɮɟɪɢɱɟɫɤɨɣ ɤɪɨɜɢ ɩɚɰɢɟɧɬɨɜ ɫ ɩɟɪɜɢɱɧɨɣ ɝɢɩɟɪɥɢɩɢɞɟɦɢɟɣ ɢ ɤɨɪɨɧɚɪɧɵɦ ɚɬɟɪɨɫɤɥɟɪɨɡɨɦ ɬɚɤɠɟ ɩɨɡɜɨɥɢɥɨ
ɨɛɧɚɪɭɠɢɬɶ ɤɨɥɨɧɢɢ ɫɬɪɨɦɚɥɶɧɵɯ ɮɢɛɪɨɛɥɚɫɬɨɩɨɞɨɛɧɵɯ ɤɥɟɬɨɤ, ɤɨɬɨɪɵɟ ɫɢɧɬɟɡɢɪɨɜɚɥɢ ɮɢɛɪɢɥɥɹɪɧɵɣ ɢ ɨɫɬɟɨɢɞɧɵɣ ɜɧɟɤɥɟɬɨɱɧɵɣ
ɦɚɬɪɢɤɫ [72]. ɗɬɢ ɞɚɧɧɵɟ ɞɚɸɬ ɨɫɧɨɜɚɧɢɟ ɩɨɥɚɝɚɬɶ, ɱɬɨ ɫɭɳɟɫɬɜɭɟɬ
ɬɟɫɧɚɹ ɜɡɚɢɦɨɫɜɹɡɶ ɦɟɠɞɭ ɪɚɡɜɢɬɢɟɦ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɢ ɩɨɜɟɞɟɧɢɟɦ
ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ-ɩɪɟɞɲɟɫɬɜɟɧɧɢɤɨɜ.
ɂɡ-ɡɚ ɨɝɪɚɧɢɱɟɧɧɨɣ ɫɩɨɫɨɛɧɨɫɬɢ ɫɟɪɞɟɱɧɨɣ ɦɵɲɰɵ ɤ ɜɨɫɫɬɚɧɨɜɥɟɧɢɸ, ɢɧɮɚɪɤɬ ɦɢɨɤɚɪɞɚ ɩɪɢɜɨɞɢɬ ɤ ɧɟɨɛɪɚɬɢɦɨɦɭ ɧɚɪɭɲɟɧɢɸ ɪɚɛɨɬɵ ɫɟɪɞɰɚ ɢ ɯɪɨɧɢɱɟɫɤɨɣ ɫɟɪɞɟɱɧɨɣ ɧɟɞɨɫɬɚɬɨɱɧɨɫɬɢ, ɧɟ ɩɨɞɞɚɸɳɟɣɫɹ ɯɢɪɭɪɝɢɱɟɫɤɨɦɭ ɢ ɮɚɪɦɚɤɨɥɨɝɢɱɟɫɤɨɦɭ ɥɟɱɟɧɢɸ. Ⱥɥɶɬɟɪɧɚɬɢ16
ɜɨɣ ɬɪɚɞɢɰɢɨɧɧɨɣ ɬɟɪɚɩɢɢ ɫɟɝɨɞɧɹ ɫɱɢɬɚɟɬɫɹ ɬɪɚɧɫɩɥɚɧɬɚɰɢɹ ɋɄ ɤɚɤ
ɷɦɛɪɢɨɧɚɥɶɧɨɝɨ, ɬɚɤ ɢ ɩɨɫɬɧɚɬɚɥɶɧɨɝɨ ɩɪɨɢɫɯɨɠɞɟɧɢɹ. ȼ ɤɚɱɟɫɬɜɟ
ɧɚɢɛɨɥɟɟ ɩɟɪɫɩɟɤɬɢɜɧɵɯ ɢɫɬɨɱɧɢɤɨɜ ɋɄ ɪɚɫɫɦɚɬɪɢɜɚɸɬɫɹ ɤɨɫɬɧɵɣ
ɦɨɡɝ, ɦɨɛɢɥɢɡɨɜɚɧɧɚɹ ɩɟɪɢɮɟɪɢɱɟɫɤɚɹ ɤɪɨɜɶ, ɚ ɬɚɤɠɟ ɩɭɩɨɜɢɧɧɚɹ
ɤɪɨɜɶ ɧɨɜɨɪɨɠɞɟɧɧɵɯ [35].
Ⱥɜɬɨɪɵ ɭɤɚɡɚɧɧɨɣ ɪɚɛɨɬɵ ɫɱɢɬɚɸɬ, ɱɬɨ ɧɟɨɛɯɨɞɢɦɨ ɜɵɹɫɧɢɬɶ,
ɤɚɤɨɣ ɢɦɟɧɧɨ ɬɢɩ ɤɥɟɬɨɤ ɭɱɚɫɬɜɭɟɬ ɜ ɪɟɝɟɧɟɪɚɰɢɢ, ɚ ɬɚɤɠɟ ɪɚɡɪɚɛɨɬɚɬɶ ɦɟɬɨɞɵ ɫɬɢɦɭɥɹɰɢɢ ɞɚɧɧɵɯ ɤɥɟɬɨɤ ɜ ɭɫɥɨɜɢɹɯ in vitro ɞɨ ɜɜɟɞɟɧɢɹ ɜ ɨɪɝɚɧɢɡɦ, ɫ ɰɟɥɶɸ ɭɫɢɥɟɧɢɹ ɢɯ ɪɟɦɨɞɟɥɢɪɭɸɳɟɝɨ ɷɮɮɟɤɬɚ.
ɗɬɢ ɷɤɫɩɟɪɢɦɟɧɬɵ ɹɜɥɹɸɬɫɹ ɨɞɧɢɦɢ ɢɡ ɩɟɪɜɵɯ ɫɜɢɞɟɬɟɥɶɫɬɜ ɩɟɪɫɩɟɤɬɢɜɧɨɫɬɢ ɧɨɜɵɯ ɩɨɞɯɨɞɨɜ ɩɨ ɫɬɢɦɭɥɹɰɢɢ ɪɟɝɟɧɟɪɚɬɢɜɧɨɢɧɞɭɤɰɢɨɧɧɵɯ ɫɜɨɣɫɬɜ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ.
Ʉɚɤ ɧɚɦ ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ, ɨɱɟɧɶ ɜɚɠɧɨ, ɱɬɨɛɵ ɛɵɥɨ ɩɪɨɞɨɥɠɟɧɨ
ɢɡɭɱɟɧɢɟ ɩɪɨɬɟɨɦɚ ɋɄ, ɜɤɥɸɱɚɹ ɜɥɢɹɧɢɟ ɧɚ ɧɟɝɨ ɮɚɤɬɨɪɨɜ ɦɢɤɪɨɨɤɪɭɠɟɧɢɹ, ɨɩɪɟɞɟɥɹɸɳɢɯ ɞɚɥɶɧɟɣɲɟɟ ɪɚɡɜɢɬɢɟ ɢ ɮɭɧɤɰɢɨɧɢɪɨɜɚɧɢɟ ɋɄ.
ɇɨ ɧɟ ɦɟɧɟɟ ɜɚɠɧɨ ɢ ɩɚɪɚɥɥɟɥɶɧɨɟ ɢɫɫɥɟɞɨɜɚɧɢɟ ɩɪɨɬɟɨɦɚ ɞɪɭɝɢɯ ɷɥɟɦɟɧɬɨɜ ɋɋɋ, ɩɚɬɨɥɨɝɢɱɟɫɤɢɟ ɢɡɦɟɧɟɧɢɹ ɜ ɤɨɬɨɪɨɣ ɧɟ ɦɨɝɭɬ ɧɟ
ɡɚɬɪɨɧɭɬɶ ɦɧɨɝɢɟ ɟɟ ɤɨɦɩɨɧɟɧɬɵ, ɜɤɥɸɱɚɹ ɝɥɚɞɤɨɦɵɲɟɱɧɵɟ ɢ ɷɧɞɨɬɟɥɢɚɥɶɧɵɟ ɤɥɟɬɤɢ. ɉɪɟɞɫɬɚɜɥɹɟɬɫɹ, ɱɬɨ ɜɵɹɜɥɟɧɢɟ ɦɨɞɢɮɢɰɢɪɭɟɦɵɯ
ɩɚɬɨɥɨɝɢɟɣ ɛɟɥɤɨɜ ɦɨɠɟɬ ɞɚɬɶ ɤɥɸɱ, ɤɚɤ ɤ ɩɨɧɢɦɚɧɢɸ ɦɟɯɚɧɢɡɦɨɜ
ɡɚɛɨɥɟɜɚɧɢɣ, ɬɚɤ ɢ ɤ ɢɯ ɥɟɱɟɧɢɸ. ȼ ɞɚɧɧɵɣ ɦɨɦɟɧɬ ɬɚɤɢɯ ɷɤɫɩɟɪɢɦɟɧɬɨɜ, ɯɚɪɚɤɬɟɪɢɡɭɟɦɵɯ ɤɚɤ «ɮɭɧɤɰɢɨɧɚɥɶɧɚɹ ɩɪɨɬɟɨɦɢɤɚ», ɜɵɩɨɥɧɟɧɨ
ɹɜɧɨ ɧɟɞɨɫɬɚɬɨɱɧɨ. Ɍɟɦ ɧɟ ɦɟɧɟɟ, ɫɨɨɬɜɟɬɫɬɜɭɸɳɟɟ ɩɨɜɟɞɟɧɢɟ ɛɟɥɤɨɜ,
ɜɤɥɸɱɚɹ ɢɡɦɟɧɟɧɢɟ ɢɯ ɤɨɥɢɱɟɫɬɜɚ, ɢɡɭɱɚɥɨɫɶ ɩɪɢ ɤɚɪɞɢɨɦɢɨɩɚɬɢɹɯ
ɱɟɥɨɜɟɤɚ ɢ ɠɢɜɨɬɧɵɯ ɢ ɜ ɪɹɞɟ ɞɪɭɝɢɯ ɫɥɭɱɚɟɜ. ɋɨɝɥɚɫɧɨ ɩɪɟɞɜɚɪɢɬɟɥɶɧɵɦ ɞɚɧɧɵɦ, ɧɚɢɛɨɥɟɟ ɨɛɟɳɚɸɳɢɦɢ ɦɚɪɤɟɪɚɦɢ ɞɥɹ ɤɚɪɞɢɨɩɪɨɬɟɨɦɢɤɢ ɦɨɝɭɬ ɛɵɬɶ ɬɪɨɩɨɧɢɧɵ, ɢɡɨɮɨɪɦɵ ɚɥɶɮɚ-1-ɮɢɛɪɢɧɨɝɟɧɚ,
ɢɡɨɮɨɪɦɵ ɚɩɨɥɢɩɨɩɪɨɬɟɢɧɚ Ⱥ-1, ɋ-ɪɟɚɤɬɢɜɧɵɣ ɛɟɥɨɤ ɢ ɞɪ. [8,105].
17
ɋ ɩɨɦɨɳɶɸ ɩɪɨɬɟɨɦɢɤɢ ɭɠɟ ɩɨɤɚɡɚɧɨ, ɱɬɨ ɨɤɢɫɥɟɧɧɵɟ Ʌɉɇɉ ɩɨɞɚɜɥɹɸɬ ɩɪɨɥɢɮɟɪɚɰɢɸ ɤɥɟɬɨɤ ɜ ɷɧɞɨɬɟɥɢɢ, ɱɬɨ ɨɛɴɹɫɧɹɟɬɫɹ, ɜɢɞɢɦɨ,
ɦɨɞɢɮɢɤɚɰɢɟɣ ɛɟɥɤɨɜ (ɮɨɫɮɨɪɢɥɢɪɨɜɚɧɢɟɦ, ɚɜɬɨɞɟɝɪɚɞɚɰɢɟɣ ɢ/ɢɥɢ ɢɡɦɟɧɟɧɧɨɣ ɷɤɫɩɪɟɫɫɢɟɣ ɧɭɤɥɟɨɮɨɫɦɢɧɚ, ɫɬɚɬɦɢɧɚ ɢ ɧɭɤɥɟɨɥɢɧɚ ɩɪɢ ɭɫɥɨɜɢɹɯ ɨɤɢɫɥɢɬɟɥɶɧɨɝɨ ɫɬɪɟɫɫɚ) [3]. ɋɥɟɞɭɟɬ ɨɬɦɟɬɢɬɶ ɬɚɤɠɟ ɪɚɛɨɬɭ
Gundry et. al. [36], ɩɨɫɜɹɳɟɧɧɭɸ ɛɟɥɤɚɦ ɩɨɜɟɪɯɧɨɫɬɢ ɋɄ ɢ ɢɯ ɩɨɬɟɧɰɢɚɥɶɧɨɣ ɪɨɥɢ ɜ ɪɟɝɟɧɟɪɚɬɢɜɧɨɣ ɦɟɞɢɰɢɧɟ ɋɋɋ.
Ɇɨɠɧɨ ɩɪɟɞɩɨɥɨɠɢɬɶ, ɱɬɨ ɜ ɪɚɡɜɢɬɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ, ɚ ɢɦɟɧɧɨ
ɜ ɩɨɩɵɬɤɟ ɥɨɤɚɥɢɡɚɰɢɢ ɢ ɥɢɤɜɢɞɚɰɢɢ ɜɨɫɩɚɥɢɬɟɥɶɧɨɝɨ ɩɪɨɰɟɫɫɚ ɜ
ɫɬɟɧɤɟ ɫɨɫɭɞɚ, ɢɫɩɨɥɶɡɭɟɬɫɹ ɭɧɢɜɟɪɫɚɥɶɧɵɣ ɦɟɯɚɧɢɡɦ ɬɤɚɧɟɜɨɣ ɪɟɝɟɧɟɪɚɰɢɢ ɫ ɭɱɚɫɬɢɟɦ ɜ ɧɟɦ ɩɨɥɢɩɨɬɟɧɬɧɵɯ ɋɄ. ɉɪɨɧɢɤɧɨɜɟɧɢɟ
ɷɬɢɯ ɭɧɢɜɟɪɫɚɥɶɧɵɯ ɤɥɟɬɨɤ ɜ ɢɧɬɢɦɭ ɢ ɩɨɫɥɟɞɭɸɳɚɹ ɪɟɚɥɢɡɚɰɢɹ
ɩɪɢɫɭɳɟɣ ɢɦ ɩɨɥɢɩɨɬɟɧɬɧɨɫɬɢ ɦɨɝɭɬ ɛɵɬɶ ɩɪɢɱɢɧɨɣ ɮɨɪɦɢɪɨɜɚɧɢɹ
ɛɥɹɲɟɤ ɪɚɡɧɨɝɨ ɝɟɧɟɡɚ. Ʌɨɤɚɥɶɧɨɟ ɦɢɤɪɨɨɤɪɭɠɟɧɢɟ ɦɨɠɟɬ ɨɩɪɟɞɟɥɹɬɶ ɞɢɮɮɟɪɟɧɰɢɪɨɜɤɭ ɫɬɜɨɥɨɜɵɯ ɤɨɥɨɧɢɟɨɛɪɚɡɭɸɳɢɯ ɤɥɟɬɨɤ ɜ
ɪɚɡɥɢɱɧɨɦ ɧɚɩɪɚɜɥɟɧɢɢ ɢ ɛɵɬɶ ɩɪɢɱɢɧɨɣ ɧɟ ɬɨɥɶɤɨ ɮɢɛɪɨɡɚ ɜ ɢɧɬɢɦɟ ɫɨɫɭɞɢɫɬɨɣ ɫɬɟɧɤɢ, ɧɨ ɢ ɯɨɧɞɪɨ- ɢɥɢ ɨɫɬɟɨɝɟɧɟɡɚ ɫ ɩɨɫɥɟɞɭɸɳɟɣ ɤɚɥɶɰɢɮɢɤɚɰɢɟɣ.
Ɉɬɦɟɬɢɦ ɜ ɷɬɨɣ ɫɜɹɡɢ, ɱɬɨ ɜ ɩɟɪɢɮɟɪɢɱɟɫɤɨɣ ɤɪɨɜɢ ɩɚɰɢɟɧɬɨɜ ɫ
ɞɨɤɭɦɟɧɬɢɪɨɜɚɧɧɵɦ ɚɬɟɪɨɫɤɥɟɪɨɡɨɦ (ɜ ɨɬɥɢɱɢɟ ɨɬ ɡɞɨɪɨɜɵɯ ɞɨɛɪɨɜɨɥɶɰɟɜ) ɩɨɤɚɡɚɧɨ ɜɵɫɨɤɨɟ ɫɨɞɟɪɠɚɧɢɟ ɰɢɪɤɭɥɢɪɭɸɳɢɯ ɩɪɟɨɫɬɟɨɤɥɚɫɬɨɜ. ɗɬɨɬ ɮɟɧɨɦɟɧ, ɩɨ-ɜɢɞɢɦɨɦɭ, ɫɜɹɡɚɧ ɫ ɩɪɨɰɟɫɫɨɦ ɤɚɥɶɰɢɮɢɤɚɰɢɢ
ɜ ɫɬɟɧɤɟ ɫɨɫɭɞɚ, ɧɟɩɨɫɪɟɞɫɬɜɟɧɧɵɦɢ ɭɱɚɫɬɧɢɤɚɦɢ ɤɨɬɨɪɨɝɨ ɹɜɥɹɸɬɫɹ
ɨɫɬɟɨɛɥɚɫɬɵ. ɉɪɟɞɩɨɥɚɝɚɟɬɫɹ, ɱɬɨ ɨɫɬɟɨɛɥɚɫɬɵ ɦɨɝɭɬ ɩɪɨɢɫɯɨɞɢɬɶ ɥɢɛɨ ɢɡ ɋɄ, ɩɪɨɧɢɤɚɸɳɢɯ ɜ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɟ ɛɥɹɲɤɢ ɢɡ ɤɪɨɜɹɧɨɝɨ
ɪɭɫɥɚ ɢɥɢ ɢɡ ɩɥɸɪɢɩɨɬɟɧɬɧɵɯ ɆɋɄ, ɤɨɬɨɪɵɟ ɨɫɬɚɸɬɫɹ ɜ ɚɪɬɟɪɢɚɥɶɧɨɣ ɫɬɟɧɤɟ ɧɚ ɷɦɛɪɢɨɧɚɥɶɧɨɣ ɫɬɚɞɢɢ ɪɚɡɜɢɬɢɹ. Ɉɫɬɟɨɛɥɚɫɬɵ, ɹɜɥɹɹɫɶ
ɜɚɠɧɵɦɢ ɤɨɦɩɨɧɟɧɬɚɦɢ «ɧɢɲɢ» ȽɋɄ, ɥɟɝɤɨ ɪɟɚɝɢɪɭɸɬ ɧɚ ɜɧɟɲɧɢɟ
18
ɫɬɢɦɭɥɵ, ɱɬɨ ɩɪɢɜɨɞɢɬ ɤ ɜɨɡɞɟɣɫɬɜɢɸ ɧɚ ȽɋɄ ɩɨɫɪɟɞɫɬɜɨɦ ɪɟɰɟɩɬɨɪɨɜ, ɰɢɬɨɤɢɧɨɜ ɢ ɮɚɤɬɨɪɨɜ ɪɨɫɬɚ.
Ʉɨɦɛɢɧɢɪɭɹ ɞɨɫɬɢɠɟɧɢɹ ɛɢɨɥɨɝɢɢ ɋɄ ɢ ɡɧɚɧɢɹ ɢɯ ɩɪɨɬɟɨɦɚ,
ɦɨɠɧɨ ɩɨɧɹɬɶ ɦɟɯɚɧɢɡɦɵ ɢɯ ɩɪɨɥɢɮɟɪɚɰɢɢ ɢ ɫɚɦɨɨɛɧɨɜɥɟɧɢɹ, ɚ ɬɚɤɠɟ ɧɚɩɪɚɜɢɬɶ ɞɢɮɮɟɪɟɧɰɢɚɰɢɸ ɜ ɠɟɥɚɟɦɨɟ ɪɭɫɥɨ. ɗɬɨ ɩɨɡɜɨɥɢɬ ɭɬɨɱɧɢɬɶ ɫɩɨɫɨɛɵ ɦɚɧɢɩɭɥɹɰɢɢ ɫ ɋɄ ɢ ɪɟɚɥɢɡɨɜɚɬɶ ɦɨɳɧɵɣ ɬɟɪɚɩɟɜɬɢɱɟɫɤɢɣ ɩɨɬɟɧɰɢɚɥ ɷɬɢɯ ɭɧɢɤɚɥɶɧɵɯ ɤɥɟɬɨɤ.
1.3. Ƚɟɦɨɩɨɷɬɢɱɟɫɤɢɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ ɤɚɤ ɨɛɴɟɤɬ ɢɫɫɥɟɞɨɜɚɧɢɹ
ɢ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɜ ɩɚɬɨɮɢɡɢɨɥɨɝɢɢ
Ƚɟɦɨɩɨɷɬɢɱɟɫɤɢɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ (ȽɋɄ) ɩɪɢɧɚɞɥɟɠɚɬ ɤ ɋɄ,
ɩɨɞɜɟɪɝɚɟɦɵɦ ɜ ɩɨɫɥɟɞɧɢɟ ɝɨɞɵ ɜɫɟ ɛɨɥɟɟ ɦɚɫɲɬɚɛɧɨɦɭ ɢɡɭɱɟɧɢɸ. Ɂɚ
ɫɩɨɫɨɛɧɨɫɬɶ ɝɟɧɟɪɢɪɨɜɚɬɶ ɛɨɥɟɟ ɩɨɥɭɞɸɠɢɧɵ ɬɢɩɨɜ ɤɥɟɬɨɤ ɤɪɨɜɢ
(ɪɢɫ. 1.1) ȽɋɄ ɩɪɢɧɹɬɨ ɧɚɡɵɜɚɬɶ ɦɭɥɶɬɢɩɨɬɟɧɬɧɵɦɢ ɋɄ [88,68,103].
Ɇɟɯɚɧɢɡɦɵ, ɩɨɫɪɟɞɫɬɜɨɦ ɤɨɬɨɪɵɯ ɨɫɭɳɟɫɬɜɥɹɟɬɫɹ ɜɡɚɢɦɨɞɟɣɫɬɜɢɟ ȽɋɄ ɫɨ ɫɜɨɢɦ ɦɢɤɪɨɨɤɪɭɠɟɧɢɟɦ, ɢɥɢ ɫ ɬ.ɧ. ɧɢɲɟɣ, ɞɨ ɫɢɯ ɩɨɪ ɩɨɧɹɬɧɵ ɞɚɥɟɤɨ ɧɟ ɩɨɥɧɨɫɬɶɸ. ȼ ɷɬɨɣ ɫɜɹɡɢ ɜɨɡɦɨɠɧɨɫɬɶ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ ȽɋɄ ɞɥɹ ɢɯ ɩɨɫɥɟɞɭɸɳɟɝɨ ɢɡɭɱɟɧɢɹ ɢ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɥɢɦɢɬɢɪɭɟɬɫɹ ɫɩɨɫɨɛɧɨɫɬɶɸ ɦɚɧɢɩɭɥɢɪɨɜɚɬɶ ɫ ɷɬɢɦɢ ɤɥɟɬɤɚɦɢ in vitro. Ⱦɨ ɫɢɯ
ɩɨɪ ɫɭɳɟɫɬɜɭɟɬ ɜɟɫɶɦɚ ɨɝɪɚɧɢɱɟɧɧɨɟ ɱɢɫɥɨ ɫɩɨɫɨɛɨɜ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ, ɤɨɬɨɪɵɟ ɩɨɡɜɨɥɹɸɬ ɩɨɞɞɟɪɠɢɜɚɬɶ ɢ ɪɚɡɦɧɨɠɚɬɶ ȽɋɄ in vitro, ɩɪɢ
ɷɬɨɦ ɫɨɯɪɚɧɹɟɬɫɹ ɧɟɩɨɥɧɨɟ ɡɧɚɧɢɟ ɨ ɜɥɢɹɧɢɢ ɪɚɡɥɢɱɧɵɯ ɭɫɥɨɜɢɣ
ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ ɧɚ ɛɟɥɤɨɜɵɣ ɫɨɫɬɚɜ ɤɥɟɬɨɤ.
ɂɧɮɨɪɦɚɰɢɹ ɨ ɫɨɫɬɚɜɟ ȽɋɄ ɜ ɢɯ ɟɫɬɟɫɬɜɟɧɧɨɦ ɫɨɫɬɨɹɧɢɢ ɦɨɝɥɚ
ɛɵ ɫɩɨɫɨɛɫɬɜɨɜɚɬɶ ɨɩɬɢɦɢɡɚɰɢɢ ɷɬɢɯ ɭɫɥɨɜɢɣ ɢ ɩɨɥɭɱɟɧɢɸ ɢɫɬɢɧɧɨ
ɝɨɦɨɝɟɧɧɨɣ ɩɨɩɭɥɹɰɢɢ ȽɋɄ. ɇɟɭɞɢɜɢɬɟɥɶɧɨ, ɱɬɨ ɦɧɨɝɢɟ ɪɚɛɨɬɵ ɩɨ
19
ȽɋɄ ɛɵɥɢ ɩɨɫɜɹɳɟɧɵ ɢɯ ɩɨɜɟɞɟɧɢɸ ɤɚɤ ɩɨɩɭɥɹɰɢɢ ɜ ɧɚɬɭɪɚɥɶɧɨɣ
ɧɢɲɟ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ, ɩɪɟɞɨɩɪɟɞɟɥɹɸɳɟɣ ɢɯ ɛɟɥɤɨɜɵɣ ɫɨɫɬɚɜ.
Ɋɢɫ. 1.1. ɋɯɟɦɚ ɝɟɦɨɩɨɷɡɚ
ɇɚɩɪɢɦɟɪ, ɦɨɠɧɨ ɨɠɢɞɚɬɶ, ɱɬɨ Jagged1 (Jag1), ɜɵɞɟɥɹɟɦɵɣ ɨɫɬɟɨɛɥɚɫɬɚɦɢ ɜ ɨɬɜɟɬ ɧɚ ɨɛɪɚɛɨɬɤɭ ɉɌȽ (ɮɪɚɝɦɟɧɬɵ 1-34), ɜɥɢɹɟɬ ɧɚ
ȽɋɄ ɩɨ ɫɢɝɧɚɥɶɧɨɦɭ ɩɭɬɢ ɱɟɪɟɡ ɪɟɰɟɩɬɨɪ Notch-1 [24, 107]. Ɍɚɤɢɦ
ɨɛɪɚɡɨɦ, Jagged1 ɹɜɥɹɟɬɫɹ ɨɞɧɢɦ ɢɡ ɧɚɢɛɨɥɟɟ ɜɚɠɧɵɯ ɮɚɤɬɨɪɨɜ, ɨɩɪɟɞɟɥɹɸɳɢɯ ɩɭɬɶ ɪɚɡɜɢɬɢɹ ȽɋɄ. ɂɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ (ɬɚɤɢɯ, ɤɚɤ
Jag1 ɢ ɞɪɭɝɢɯ, ɫɜɹɡɚɧɧɵɯ ɫ Notch-1), ɧɚɪɹɞɭ ɫ ɭɬɨɱɧɟɧɢɟɦ ɪɨɥɢ ɞɪɭɝɢɯ ɜɧɟɲɧɢɯ ɮɚɤɬɨɪɨɜ, ɩɨɡɜɨɥɹɟɬ ɨɩɪɟɞɟɥɢɬɶ ɜɫɟ ɜɨɡɦɨɠɧɨɫɬɢ ɤɨɧɬɪɨɥɹ ȽɋɄ.
20
ȼɧɟɲɧɢɟ ɮɚɤɬɨɪɵ, ɭɱɚɫɬɜɭɸɳɢɟ ɜ ɪɟɝɭɥɹɰɢɢ ȽɋɄ, ɹɜɥɹɸɬɫɹ ɱɚɫɬɶɸ ɧɢɲɢ ɋɄ. ɂɫɫɥɟɞɨɜɚɧɢɹ ɩɨ ɯɨɭɦɢɧɝɭ ȽɋɄ, ɦɟɱɟɧɵɯ ɡɟɥɟɧɵɦ
ɮɥɭɨɪɟɫɰɢɪɭɸɳɢɦ ɛɟɥɤɨɦ (GFP), ɩɨɫɥɟ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ ɭɤɚɡɵɜɚɸɬ
ɧɚ ɩɨɜɟɪɯɧɨɫɬɶ ɷɧɞɨɫɬɢɥɹ ɤɚɤ ɜɨɡɦɨɠɧɭɸ ɧɢɲɭ ɋɄ [66]. ɇɨ ɫɚɦɵɣ
ɫɟɪɶɟɡɧɵɣ ɜɵɜɨɞ ɢɡ ɷɬɢɯ ɷɤɫɩɟɪɢɦɟɧɬɨɜ ɩɨ ɯɨɭɦɢɧɝɭ – ɜɚɠɧɨɫɬɶ ɨɫɬɟɨɛɥɚɫɬɨɜ ɜ ɮɭɧɤɰɢɨɧɢɪɨɜɚɧɢɢ ɧɢɲɢ ȽɋɄ ɜ ɤɨɫɬɧɨɦ ɦɨɡɝɟ [24, 107].
1.3.1. Ɋɟɝɭɥɹɬɨɪɵ ȽɋɄ
ȼ ɧɚɫɬɨɹɳɟɟ ɜɪɟɦɹ ɜɚɠɧɨɫɬɶ Notch ɜ ɫɢɝɧɚɥɢɡɚɰɢɢ ɩɪɢ ɝɟɦɚɬɨɩɨɷɡɟ
ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ
ɧɟɫɨɦɧɟɧɧɨɣ.
ɗɤɫɩɪɟɫɫɢɹ
ɚɤɬɢɜɢɪɨɜɚɧɧɨɝɨ
Notch1, ɨɩɨɫɪɟɞɨɜɚɧɧɚɹ ɪɟɬɪɨɜɢɪɭɫɨɦ, ɭɜɟɥɢɱɢɜɚɥɚ ɫɤɨɪɨɫɬɶ ɫɚɦɨɨɛɧɨɜɥɟɧɢɹ ɤɥɟɬɨɤ-ɩɪɟɞɲɟɫɬɜɟɧɧɢɤɨɜ ɝɟɦɨɩɨɷɡɚ ɜ ɩɪɢɫɭɬɫɬɜɢɢ ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɯ ɰɢɬɨɤɢɧɨɜ, ɱɬɨ ɭɤɚɡɵɜɚɟɬ ɧɚ ɩɨɬɟɧɰɢɚɥɶɧɭɸ ɫɩɨɫɨɛɧɨɫɬɶ
Notch ɭɫɢɥɢɜɚɬɶ ɫɚɦɨɨɛɧɨɜɥɟɧɢɟ ɋɄ [93].
ȼ
ɞɪɭɝɢɯ
ɪɚɛɨɬɚɯ
ɩɨɤɚɡɚɧɨ,
ɱɬɨ
ɤɨɥɢɱɟɫɬɜɨ
ɤɥɟɬɨɤ-
ɩɪɟɞɲɟɫɬɜɟɧɧɢɤɨɜ ɝɟɦɨɩɨɷɡɚ ɜɨɡɪɚɫɬɚɥɨ ɩɨɫɥɟ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ ɫ ɥɢɝɚɧɞɨɦ ɪɟɰɟɩɬɨɪɚ Notch, ɩɪɢɫɭɬɫɬɜɭɸɳɢɦ ɧɚ ɩɨɜɟɪɯɧɨɫɬɢ ɤɥɟɬɨɤ, ɢɥɢ
ɫ ɥɢɝɚɧɞɚɦɢ Notch, ɬɚɤɢɦɢ, ɤɚɤ Delta-1, Jagged-1, ɢɥɢ Jagged-2, ɜ ɪɚɫɬɜɨɪɟ [37, 43, 46,45, 47, 89,94, 100].
ɉɪɢ
ɢɧɤɭɛɚɰɢɢ
ɦɵɲɢɧɵɯ
ɝɟɦɚɬɨɩɨɷɬɢɱɟɫɤɢɯ
ɤɥɟɬɨɤ-
ɩɪɟɞɲɟɫɬɜɟɧɧɢɤɨɜ, ɫɬɢɦɭɥɢɪɨɜɚɧɧɵɯ ɰɢɬɨɤɢɧɚɦɢ, ɫ Delta-1, ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɵɦ ɧɚ ɩɨɜɟɪɯɧɨɫɬɢ ɩɥɚɫɬɢɤɨɜɵɯ ɱɚɲɟɤ, ɧɚɛɥɸɞɚɥɚɫɶ ɢɯ ɛɵɫɬɪɚɹ ɷɤɫɩɚɧɫɢɹ, ɚ ɬɪɚɧɫɩɥɚɧɬɚɰɢɹ ɬɚɤɢɯ ɤɭɥɶɬɢɜɢɪɨɜɚɧɧɵɯ ɤɥɟɬɨɤ ɩɪɢɜɨɞɢɥɚ ɤ ɥɨɝɚɪɢɮɦɢɱɟɫɤɨɦɭ ɪɨɫɬɭ ɱɢɫɥɚ ɤɨɪɨɬɤɨɠɢɜɭɳɢɯ ɤɥɟɬɨɤ,
ɜɨɫɫɬɚɧɚɜɥɢɜɚɸɳɢɯ ɤɨɫɬɧɵɣ ɦɨɡɝ [95]. Ɉɞɧɚɤɨ ɢɦɟɧɧɨ Jagged-1, ɚ ɧɟ
Delta-1, ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ ɝɥɚɜɧɵɦ ɥɢɝɚɧɞɨɦ ɪɟɰɟɩɬɨɪɚ Notch, ɷɤɫɩɪɟɫɫɢɪɭɟɦɵɦ ɫɬɪɨɦɚɥɶɧɵɦɢ ɤɥɟɬɤɚɦɢ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ [70,94].
21
Vas ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ [96] ɩɨɤɚɡɚɥ, ɱɬɨ ɢɦɦɨɛɢɥɢɡɚɰɢɹ Jagged-1
ɥɢɛɨ ɧɚ ɫɬɪɨɦɚɥɶɧɨɦ ɫɥɨɟ, ɥɢɛɨ ɧɚ ɦɢɤɪɨɫɮɟɪɚɯ Sepharose-4B ɧɟɨɛɯɨɞɢɦɚ ɞɥɹ ɢɧɞɭɤɰɢɢ ɫɚɦɨɨɛɧɨɜɥɟɧɢɹ ȽɋɄ. Ɂɚɦɟɬɢɦ, ɱɬɨ ɫɜɨɛɨɞɧɵɣ, ɪɚɫɬɜɨɪɢɦɵɣ Jagged-1 ɨɛɥɚɞɚɟɬ ɞɨɦɢɧɚɧɬɧɨ-ɨɬɪɢɰɚɬɟɥɶɧɵɦ
ɞɟɣɫɬɜɢɟɦ ɧɚ ɫɚɦɨɨɛɧɨɜɥɟɧɢɟ ɜ ɤɨɦɩɚɪɬɦɟɧɬɟ ɪɚɧɧɢɯ ɩɪɨɝɟɧɢɬɨɪɧɵɯ ɤɥɟɬɨɤ, ɩɪɟɞɩɨɥɨɠɢɬɟɥɶɧɨ ɡɚ ɫɱɟɬ ɫɟɤɜɟɫɬɢɪɨɜɚɧɢɹ ɪɟɰɟɩɬɨɪɚ
Notch ɢ ɩɪɟɞɨɬɜɪɚɳɟɧɢɹ ɜɡɚɢɦɨɞɟɣɫɬɜɢɹ Notch ɫ ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɵɦ ɥɢɝɚɧɞɨɦ [96].
ɏɨɬɹ ɦɧɨɝɨɱɢɫɥɟɧɧɵɟ ɞɚɧɧɵɟ ɫɜɢɞɟɬɟɥɶɫɬɜɭɸɬ ɨ ɜɨɜɥɟɱɟɧɢɢ
Notch-ɫɢɝɧɚɥɢɡɚɰɢɢ ɜ ɩɨɞɞɟɪɠɚɧɢɟ ɢ/ɢɥɢ ɫɚɦɨɨɛɧɨɜɥɟɧɢɟ ȽɋɄ, ɧɟɬ
ɨɞɧɨɡɧɚɱɧɵɯ ɞɨɤɚɡɚɬɟɥɶɫɬɜ ɥɢɝɚɧɞ-ɢɧɞɭɰɢɪɨɜɚɧɧɨɣ ɫɚɦɨɨɛɧɨɜɥɹɸɳɟɣɫɹ ɩɪɨɥɢɮɟɪɚɰɢɢ ȽɋɄ, ɜɟɞɭɳɟɣ ɤ ɢɯ ɞɨɥɝɨɫɪɨɱɧɨɣ ɫɩɨɫɨɛɧɨɫɬɢ ɤ
ɪɟɩɨɩɭɥɹɰɢɢ [96].
Kertesz ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ [48] ɩɨɤɚɡɚɥ, ɱɬɨ ɢɧɞɭɰɢɪɨɜɚɧɧɚɹ ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɵɦ Jagged-1 ɚɤɬɢɜɚɰɢɹ Notch ɜ ɤɭɥɶɬɭɪɟ ɤɥɟɬɨɤ ɤɨɫɬɧɨɝɨ
ɦɨɡɝɚ ɥɢɧɟɣɧɵɯ ɦɵɲɟɣ ɫɭɳɟɫɬɜɟɧɧɨ ɭɜɟɥɢɱɢɜɚɟɬ ɫɩɨɫɨɛɧɨɫɬɶ ɤ ɪɟɩɨɩɭɥɹɰɢɢ ȽɋɄ ɜ ɩɪɢɫɭɬɫɬɜɢɢ ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɯ ɰɢɬɨɤɢɧɨɜ, ɚ ɢɦɟɧɧɨ
ɮɚɤɬɨɪɚ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ (SCF), ɥɢɝɚɧɞɚ Flk-2/Flt-3 (FL) ɢ ɬɪɨɦɛɨɩɪɨɬɟɢɧɚ (TPO) [48].
ɇɚɤɨɩɥɟɧɢɟ ȽɋɄ ɦɨɠɟɬ ɛɵɬɶ ɬɚɤɠɟ ɞɨɫɬɢɝɧɭɬɨ ɜ ɤɭɥɶɬɭɪɟ in
vitro (14 ɞɧɟɣ) ɦɵɲɢɧɵɯ ɤɥɟɬɨɤ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɜ ɫɪɟɞɟ ɫ ɞɨɛɚɜɥɟɧɢɟɦ ɬɪɟɯ ɪɚɧɟɟ ɭɩɨɦɹɧɭɬɵɯ ɰɢɬɨɤɢɧɨɜ (SCF, ɥɢɝɚɧɞɚ Flk-2/Flt-3, TPO)
ɢ ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɨɝɨ ɥɢɝɚɧɞɚ Notch (Jagged-1) ɜ ɮɨɪɦɟ ɦɢɤɪɨɫɮɟɪ
Sepharose-4B, ɩɨɤɪɵɬɵɯ Jagged-1 («Jag1 ɦɢɤɪɨɫɮɟɪ») [96].
Ⱥɛɫɨɥɸɬɧɨɟ ɱɢɫɥɨ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɤɥɟɬɨɤ ɫɨ ɫɩɨɫɨɛɧɨɫɬɶɸ ɤ
ɞɨɥɝɨɫɪɨɱɧɨɣ ɪɟɩɨɩɭɥɹɰɢɢ ɭɜɟɥɢɱɢɜɚɥɨɫɶ ɜ 10–20 ɪɚɡ ɜ ɩɪɢɫɭɬɫɬɜɢɢ ɦɭɥɶɬɢɜɚɥɟɧɬɧɨɝɨ ɥɢɝɚɧɞɚ Notch. ɗɬɢ ɪɟɡɭɥɶɬɚɬɵ ɭɤɚɡɵɜɚɸɬ ɧɚ
ɤɨɦɛɢɧɢɪɨɜɚɧɧɨɟ ɜɥɢɹɧɢɟ Notch ɢ ɰɢɬɨɤɢɧɨɜ ɧɚ ɩɭɬɢ ɫɢɝɧɚɥɢɡɚ22
ɰɢɢ, ɪɟɝɭɥɢɪɭɸɳɢɟ ɪɚɡɜɢɬɢɟ ȽɋɄ, ɚ ɬɚɤɠɟ ɧɚ ɩɨɬɟɧɰɢɚɥɶɧɭɸ ɪɨɥɶ
ɥɢɝɚɧɞɚ Notch ɜ ɜɨɡɪɚɫɬɚɧɢɢ ȽɋɄ ɩɪɢ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ ɋɄ ɜ ɤɥɢɧɢɤɟ
[48]. ɗɮɮɟɤɬɵ ɨɫɬɟɨɛɥɚɫɬɨɜ ɧɚ ȽɋɄ ɹɜɥɹɸɬɫɹ ɬɨɣ ɫɬɚɪɬɨɜɨɣ ɬɨɱɤɨɣ,
ɢɫɯɨɞɹ ɢɡ ɤɨɬɨɪɨɣ ɩɪɨɬɟɨɦɢɤɚ ɞɚɟɬ ɜɨɡɦɨɠɧɨɫɬɶ ɢɫɫɥɟɞɨɜɚɬɶ ɪɨɥɶ
ɨɫɬɟɨɛɥɚɫɬɨɜ ɜ ɩɪɨɥɢɮɟɪɚɰɢɢ ȽɋɄ.
ɉɨɢɫɤ ɮɚɤɬɨɪɨɜ, ɤɨɬɨɪɵɟ ɫɩɨɫɨɛɫɬɜɭɸɬ ɪɚɡɦɧɨɠɟɧɢɸ ȽɋɄ ɜ ɤɭɥɶɬɭɪɟ, ɩɪɨɜɨɞɢɥɫɹ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɨɝɨ Jag1 [96]. ɉɪɢ
ɷɬɨɦ Jag1-ɫɮɟɪɵ ɢɦɢɬɢɪɨɜɚɥɢ ɞɟɣɫɬɜɢɟ ɨɫɬɟɨɛɥɚɫɬɨɜ ɜ ɧɢɲɟ ȽɋɄ. ɇɚɛɥɸɞɚɟɦɵɟ ɷɮɮɟɤɬɵ ɭɫɢɥɢɥɢ ɩɨɡɢɰɢɢ ɬɟɯ, ɤɬɨ ɫɱɢɬɚɟɬ, ɱɬɨ ɩɨɧɢɦɚɧɢɟ
ɪɨɥɢ ɦɢɤɪɨɨɤɪɭɠɟɧɢɹ ȽɋɄ ɫɨɜɟɪɲɟɧɧɨ ɧɟɨɛɯɨɞɢɦɨ ɞɥɹ ɩɨɥɭɱɟɧɢɹ ɜɨɡɦɨɠɧɨɫɬɢ ɭɩɪɚɜɥɟɧɢɹ ɪɚɡɦɧɨɠɟɧɢɟɦ ȽɋɄ in vitro. Ɉɩɪɟɞɟɥɢɜ ɧɢɲɭ ɤɚɤ
ɞɟɬɟɪɦɢɧɚɧɬɭ ɜ ɪɟɝɭɥɹɰɢɢ ȽɋɄ, ɪɨɥɶ ɜɧɭɬɪɟɧɧɢɯ ɫɢɝɧɚɥɨɜ ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ ɫ ɧɨɜɨɣ ɬɨɱɤɢ ɡɪɟɧɢɹ, ɧɟ ɬɨɥɶɤɨ ɤɚɤ ɪɟɝɭɥɢɪɭɸɳɢɯ ɫɚɦɢ ɩɨ ɫɟɛɟ, ɧɨ
ɢ ɜɨ ɜɡɚɢɦɨɞɟɣɫɬɜɢɢ ɫ ɞɪɭɝɢɦɢ ɢɧɫɬɪɭɦɟɧɬɚɦɢ ɞɥɹ ɫɨɜɦɟɫɬɧɨɝɨ ɜɥɢɹɧɢɹ ɤɨɦɩɨɧɟɧɬɨɜ ɧɢɲɢ ɧɚ ɮɭɧɤɰɢɨɧɢɪɨɜɚɧɢɟ ɋɄ.
1.3.2. Ⱥɥɶɬɟɪɧɚɬɢɜɧɵɟ ɢɫɬɨɱɧɢɤɢ ȽɋɄ
ɂɫɩɨɥɶɡɨɜɚɧɢɟ ȽɋɄ ɧɟ ɢɡ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ, ɚ ɢɡ ɞɪɭɝɢɯ ɢɫɬɨɱɧɢɤɨɜ
ɩɪɢɜɟɥɨ ɤ ɫɞɜɢɝɭ ɬɟɪɦɢɧɨɥɨɝɢɢ ɨɬ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɤ
ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ ȽɋɄ (Ɍ-ȽɋɄ) [87]. Ɉɛɧɚɪɭɠɟɧɢɟ ȽɋɄ ɜ ɩɭɩɨɜɢɧɧɨɣ
ɤɪɨɜɢ ɞɚɥɨ ɬɨɥɱɨɤ ɤ ɢɫɩɨɥɶɡɨɜɚɧɢɸ ɷɬɢɯ ɤɥɟɬɨɤ ɜ Ɍ-ȽɋɄ, ɨɛ ɭɫɩɟɲɧɨɫɬɢ ɤɨɬɨɪɨɣ ɫɨɨɛɳɢɥɢ Gluckman ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ ɜ 1989 ɝ. [87, 32].
Ȼɚɧɤɢ ɡɚɦɨɪɨɠɟɧɧɵɯ ɤɥɟɬɨɤ ɢɡ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ (ɉɄ) ɫɟɣɱɚɫ –
ɨɛɵɱɧɨɟ ɹɜɥɟɧɢɟ [32,33, 75,87]. ɋɨɨɛɳɚɟɬɫɹ, ɱɬɨ ȽɋɄ ɢɡ ɉɄ ɦɨɝɭɬ
ɛɵɬɶ ɢɦɦɭɧɨɥɨɝɢɱɟɫɤɢ ɧɟɡɪɟɥɵ ɢ ɧɟ ɜɵɡɵɜɚɬɶ ɡɚɛɨɥɟɜɚɧɢɹ «ɬɪɚɧɫɩɥɚɧɬɚɬ ɩɪɨɬɢɜ ɯɨɡɹɢɧɚ» (GVHD), ɢɦɟɬɶ ɜɵɫɨɤɭɸ ɩɪɨɥɢɮɟɪɚɬɢɜɧɭɸ
ɢ ɤɨɥɨɧɢɟɨɛɪɚɡɭɸɳɭɸ ɫɩɨɫɨɛɧɨɫɬɶ ɢ ɪɟɚɝɢɪɨɜɚɬɶ ɧɚ ɮɚɤɬɨɪɵ ɪɨɫɬɚ
23
[87]. ȼ ɨɬɥɢɱɢɟ ɨɬ ɤɥɟɬɨɤ ɢɡ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ, ɬɪɚɧɫɩɥɚɧɬɚɰɢɹ ȽɋɄ
ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ ɦɟɧɟɟ ɩɨɞɜɟɪɠɟɧɧɨɣ ɨɫɥɨɠɧɟɧɢɹɦ [34, 87].
ȽɋɄ ɢɡ ɉɄ ɨɛɵɱɧɨ ɩɨɥɭɱɚɸɬ ɩɪɢ ɪɨɠɞɟɧɢɢ ɪɟɛɟɧɤɚ. Ɂɚɬɟɦ ȽɋɄ
ɯɪɚɧɹɬ ɜ ɛɚɧɤɟ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɞɥɹ ɩɨɫɥɟɞɭɸɳɟɝɨ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɜ
ɬɟɪɚɩɟɜɬɢɱɟɫɤɢɯ ɰɟɥɹɯ. ɗɬɢ ɤɥɟɬɤɢ ɦɨɝɭɬ ɩɪɢɦɟɧɹɬɶɫɹ ɞɥɹ ɜɨɡɞɟɣɫɬɜɢɹ ɤɚɤ ɧɚ ɫɚɦɢɯ ɞɨɧɨɪɨɜ, ɬɚɤ ɢ ɧɚ ɞɪɭɝɢɯ ɩɚɰɢɟɧɬɨɜ, ɚ ɬɚɤɠɟ ɜ ɢɫɫɥɟɞɨɜɚɬɟɥɶɫɤɢɯ ɰɟɥɹɯ.
Ɉɫɧɨɜɧɵɦ ɦɚɪɤɟɪɨɦ ȽɋɄ ɹɜɥɹɟɬɫɹ CD34 – ɛɟɥɨɤ, ɩɪɢɫɭɬɫɬɜɭɸɳɢɣ ɧɚ ɢɯ ɩɨɜɟɪɯɧɨɫɬɢ ɜɦɟɫɬɟ ɫ ɧɟɤɨɬɨɪɵɦɢ ɞɪɭɝɢɦɢ ɦɨɥɟɤɭɥɚɦɢ
(ɧɚɩɪɢɦɟɪ, ɪɟɰɟɩɬɨɪɨɦ ɞɥɹ ɬ.ɧ. ɮɚɤɬɨɪɚ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ). ɉɨɞɨɛɧɵɣ
ɮɟɧɨɬɢɩ ɯɚɪɚɤɬɟɪɢɡɭɟɬ ȽɋɄ ɜɧɟ ɡɚɜɢɫɢɦɨɫɬɢ ɨɬ ɢɯ ɢɫɬɨɱɧɢɤɚ: ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ, ɩɟɪɢɮɟɪɢɱɟɫɤɨɣ ɢɥɢ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ. Ⱥ ɜɨɬ ɩɨ ɫɩɨɫɨɛɧɨɫɬɢ ɤ ɩɪɨɥɢɮɟɪɚɰɢɢ ɢ ɮɨɪɦɢɪɨɜɚɧɢɸ ɤɨɥɨɧɢɣ ɩɪɢ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɢ in vitro ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ ɡɧɚɱɢɬɟɥɶɧɨ ɩɪɟɜɨɫɯɨɞɹɬ ɤɥɟɬɤɢ ɢɡ ɞɪɭɝɢɯ ɢɫɬɨɱɧɢɤɨɜ.
Ʌɢɦɢɬɢɪɭɸɳɢɣ ɮɚɤɬɨɪ ɞɥɹ ɩɨɥɭɱɟɧɢɹ ɞɨɫɬɚɬɨɱɧɨɝɨ ɤɨɥɢɱɟɫɬɜɚ
ȽɋɄ – ɢɯ ɤɨɥɢɱɟɫɬɜɨ ɜ ɨɛɪɚɡɰɚɯ, ɫɨɛɪɚɧɧɵɯ ɩɪɢ ɪɨɠɞɟɧɢɢ ɪɟɛɟɧɤɚ.
ɉɪɢɡɧɚɧɧɵɦ ɦɟɞɢɰɢɧɫɤɢɦ ɮɚɤɬɨɦ ɹɜɥɹɟɬɫɹ ɢɯ ɩɪɢɝɨɞɧɨɫɬɶ ɬɨɥɶɤɨ ɞɥɹ
ɬɟɪɚɩɢɢ ɩɚɰɢɟɧɬɨɜ ɫ ɜɟɫɨɦ 50 ɤɝ ɢɥɢ ɦɟɧɟɟ, ɬ.ɟ. ɞɥɹ ɞɟɬɟɣ ɜ ɜɨɡɪɚɫɬɟ
ɩɪɢɦɟɪɧɨ 14 ɥɟɬ [20]. ȼ ɷɬɨɣ ɫɜɹɡɢ ɰɟɥɶɸ ɫɩɟɰɢɚɥɢɫɬɨɜ ɩɨ ɫɬɜɨɥɨɜɵɦ
ɤɥɟɬɤɚɦ ɹɜɥɹɟɬɫɹ ɜɵɹɜɥɟɧɢɟ ɮɚɤɬɨɪɨɜ, ɪɟɝɭɥɢɪɭɸɳɢɯ ɮɭɧɤɰɢɨɧɢɪɨɜɚɧɢɟ ɋɄ ɜ ɢɯ ɟɫɬɟɫɬɜɟɧɧɨɦ ɨɤɪɭɠɟɧɢɢ. ɗɬɨ – ɩɭɬɶ ɤ ɦɚɧɢɩɭɥɢɪɨɜɚɧɢɸ
ɫ ɋɄ, ɢ ɩɪɨɬɟɨɦɢɤɚ ɫɩɨɫɨɛɧɚ ɩɪɨɬɨɪɢɬɶ ɟɝɨ.
Ɋɚɡɦɧɨɠɟɧɢɟ ȽɋɄ ɧɟ ɬɨɥɶɤɨ ɞɚɫɬ ɜɨɡɦɨɠɧɨɫɬɶ ɩɪɢɦɟɧɢɬɶ ɬɪɚɧɫɩɥɚɧɬɚɰɢɸ ȽɋɄ ɞɥɹ ɜɡɪɨɫɥɵɯ, ɧɨ ɢ ɩɨɡɜɨɥɢɬ ɞɨɫɬɢɱɶ ɞɪɭɝɢɯ ɤɥɢɧɢɱɟɫɤɢɯ ɩɪɟɢɦɭɳɟɫɬɜ ɞɥɹ ɪɟɰɢɩɢɟɧɬɨɜ. Ʉɥɟɬɨɱɧɚɹ ɞɨɡɚ ɬɪɚɧɫɩɥɚɧɬɚɬɚ
ɉɄ ɫɨɯɪɚɧɹɟɬ ɤɥɸɱɟɜɨɟ ɡɧɚɱɟɧɢɟ ɞɥɹ ɫɤɨɪɨɫɬɢ ɩɪɢɠɢɜɥɟɧɢɹ ɢ ɜɵɠɢɜɚɧɢɹ. Ɇɢɧɢɦɚɥɶɧɨɣ ɞɨɡɨɣ ɹɞɟɪɧɵɯ ɤɥɟɬɨɤ ɹɜɥɹɟɬɫɹ ɜɟɥɢɱɢɧɚ
24
2,0×107 ɧɚ ɨɞɢɧ ɤɝ ɜɟɫɚ ɬɟɥɚ ɪɟɰɢɩɢɟɧɬɚ ɞɥɹ ɭɫɩɟɲɧɨɣ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ, ɫ ɭɱɟɬɨɦ ɬɨɝɨ, ɱɬɨ ɜ ɫɪɟɞɧɟɦ ɨɞɧɨ ɜɡɹɬɢɟ ɩɨɪɰɢɢ ɤɪɨɜɢ ɢɡ ɩɭɩɨɜɢɧɵ ɞɚɟɬ 1×109 ɧɚ ɨɞɢɧ ɤɝ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɨɞɧɨɤɪɚɬɧɨɟ, ɜɡɹɬɢɟ ɚɭɬɨɥɨɝɢɱɧɨɣ ɤɪɨɜɢ ɧɟɞɨɫɬɚɬɨɱɧɨ ɞɥɹ ɥɸɛɵɯ ɩɚɰɢɟɧɬɨɜ, ɜɟɫ ɤɨɬɨɪɵɯ
ɩɪɟɜɵɲɚɟɬ 50 ɤɝ. ɇɟɨɛɯɨɞɢɦɨ ɩɪɨɜɟɞɟɧɢɟ ɞɚɥɶɧɟɣɲɢɯ ɢɫɫɥɟɞɨɜɚɧɢɣ ɩɨ ɪɚɡɦɧɨɠɟɧɢɸ ȽɋɄ ex vivo, ɜɤɥɸɱɚɹ ɬɪɚɧɫɩɥɚɧɬɚɰɢɸ ɦɧɨɝɨɤɪɚɬɧɵɯ ɜɡɹɬɢɣ ɤɪɨɜɢ ɢɡ ɩɭɩɨɜɢɧɵ [20]. ɂɫɩɨɥɶɡɨɜɚɧɢɟ ɞɜɭɯ ɜɡɹɬɢɣ ɤɪɨɜɢ ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ ɩɪɢɟɦɥɟɦɵɦ ɪɟɲɟɧɢɟɦ, ɨɞɧɚɤɨ ɱɚɫɬɨ ɛɵɜɚɟɬ ɬɪɭɞɧɨ ɧɚɣɬɢ ɷɬɢ ɞɜɚ ɨɛɪɚɡɰɚ ɤɪɨɜɢ ɞɥɹ ɩɚɰɢɟɧɬɚ ɢ ɨɫɭɳɟɫɬɜɢɬɶ ɭɫɩɟɲɧɨɟ ɩɪɢɠɢɜɥɟɧɢɟ.
ɇɟɨɛɯɨɞɢɦɨɫɬɶ ɜ ɪɚɡɦɧɨɠɟɧɢɢ ȽɋɄ ɜ ɭɫɥɨɜɢɹɯ ɤɭɥɶɬɭɪɵ ɨɱɟɜɢɞɧɚ, ɨɫɨɛɟɧɧɨ ɟɫɥɢ ɫɭɳɟɫɬɜɭɟɬ ɩɨɬɪɟɛɧɨɫɬɶ ɢɫɩɨɥɶɡɨɜɚɬɶ ɋɄ ɧɨɜɨɪɨɠɞɟɧɧɨɝɨ ɞɥɹ ɩɨɫɥɟɞɭɸɳɟɝɨ ɢɯ ɩɪɢɦɟɧɟɧɢɹ ɜ ɛɨɥɟɟ ɡɪɟɥɨɦ ɜɨɡɪɚɫɬɟ. ɉɪɢɦɟɧɟɧɢɟ ɬɚɤɢɯ ɤɥɟɬɨɤ – ɨɛɧɚɞɟɠɢɜɚɸɳɚɹ ɩɟɪɫɩɟɤɬɢɜɚ, ɨɞɧɚɤɨ
ɧɟɨɛɯɨɞɢɦɨ ɩɨɦɧɢɬɶ, ɱɬɨ, ɧɚɪɹɞɭ ɫ ɦɨɧɢɬɨɪɢɪɨɜɚɧɢɟɦ ɤɭɥɶɬɭɪɵ ɤɥɟɬɨɤ, ɫɥɟɞɭɟɬ ɢɦɟɬɶ ɪɟɮɟɪɟɧɫɧɵɟ ɬɨɱɤɢ ɞɥɹ ɤɨɧɬɪɨɥɹ ɜɫɟɯ ɩɚɪɚɦɟɬɪɨɜ
ɫɢɫɬɟɦɵ, ɢ ɨɞɧɨɣ ɢɡ ɬɚɤɢɯ ɬɨɱɟɤ ɹɜɥɹɟɬɫɹ ɩɪɨɬɟɨɦ. ɇɟɜɨɡɦɨɠɧɨ ɢɡɛɟɠɚɬɶ ɢɡɦɟɧɟɧɢɹ ɛɟɥɤɚ ɩɪɢ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɢ ɤɥɟɬɨɤ. Ɉɞɢɧ ɢɡ ɫɩɨɫɨɛɨɜ
ɤɨɧɬɪɨɥɹ ɡɚ ɯɨɞɨɦ ɷɬɢɯ ɢɡɦɟɧɟɧɢɣ – ɢɫɩɨɥɶɡɨɜɚɧɢɟ ɩɪɨɬɟɨɦɢɤɢ. Ɋɟɮɟɪɟɧɫɧɨɣ ɬɨɱɤɨɣ ɜ ɷɬɨɦ ɫɥɭɱɚɟ ɛɭɞɟɬ ɹɜɥɹɬɶɫɹ ɩɪɨɬɟɨɦ ȽɋɄ, ɜɵɞɟɥɟɧɧɵɣ ɢɡ ɨɛɪɚɡɰɚ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ.
1.3.3. Ʉɥɢɧɢɱɟɫɤɚɹ ɷɮɮɟɤɬɢɜɧɨɫɬɶ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ
Ⱦɨɫɬɭɩɧɨɫɬɶ ɉɄ ɤɚɤ ɚɥɶɬɟɪɧɚɬɢɜɵ ɤɨɫɬɧɨɦɭ ɦɨɡɝɭ ɜ ɤɚɱɟɫɬɜɟ
ɢɫɬɨɱɧɢɤɚ ȽɋɄ ɞɥɹ ɚɥɥɨɝɟɧɧɨɣ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ ɢɦɟɟɬ ɪɹɞ ɩɨɬɟɧɰɢɚɥɶɧɵɯ ɩɪɟɢɦɭɳɟɫɬɜ ɤɚɤ ɞɥɹ ɞɟɬɟɣ, ɬɚɤ ɢ ɞɥɹ ɜɡɪɨɫɥɵɯ ɜ ɤɥɢɧɢɱɟ-
25
ɫɤɨɣ ɩɪɚɤɬɢɤɟ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɞɪɭɝɢɦɢ ɢɫɬɨɱɧɢɤɚɦɢ ɚɥɥɨɝɟɧɧɵɯ
ȽɋɄ [13,87].
ɗɬɢ ɩɪɟɢɦɭɳɟɫɬɜɚ ɜɤɥɸɱɚɸɬ ɜ ɫɟɛɹ ɛɨɥɟɟ ɛɵɫɬɪɭɸ ɞɨɫɬɭɩɧɨɫɬɶ
ɦɚɬɟɪɢɚɥɚ, ɤɨɝɞɚ ɩɚɰɢɟɧɬɵ ɩɨɞɜɟɪɝɚɸɬɫɹ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ ɪɚɧɟɟ, ɱɟɦ
ɬɟ, ɤɨɬɨɪɵɟ ɩɨɥɭɱɚɸɬ ɬɪɚɧɫɩɥɚɧɬɚɬ ɢɡ ɤɥɟɬɨɤ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ [13].
Ʉɪɨɦɟ ɬɨɝɨ, ɥɟɝɱɟ ɪɟɲɚɟɬɫɹ ɩɪɨɛɥɟɦɚ ɬɤɚɧɟɜɨɣ ɧɟɫɨɜɦɟɫɬɢɦɨɫɬɢ ɭ
ɞɨɧɨɪɚ ɢ ɪɟɰɢɩɢɟɧɬɚ, ɱɟɦ ɩɪɢ ɢɫɩɨɥɶɡɨɜɚɧɢɢ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɢɥɢ ɩɟɪɢɮɟɪɢɱɟɫɤɨɣ ɤɪɨɜɢ [13].
ɋɭɳɟɫɬɜɭɸɬ ɢ ɧɟɞɨɫɬɚɬɤɢ ɩɪɢ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ, ɜɤɥɸɱɚɹ ɧɟɞɨɫɬɭɩɧɨɫɬɶ ɦɚɬɟɪɢɚɥɚ ɞɥɹ ɩɨɫɥɟɞɭɸɳɢɯ ɜɜɟɞɟɧɢɣ ɩɚɰɢɟɧɬɭ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɢ/ɢɥɢ ɥɢɦɮɨɰɢɬɨɜ ɨɬ ɞɨɧɨɪɚ ɩɪɢ ɧɟɭɞɚɱɧɨɣ
ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ ɢ ɧɢɡɤɨɟ ɤɨɥɢɱɟɫɬɜɨ ȽɋɄ ɜ ɟɞɢɧɨɦ ɨɛɪɚɡɰɟ, ɱɬɨ ɦɨɠɟɬ ɜɵɡɜɚɬɶ ɨɬɫɪɨɱɟɧɧɨɟ ɩɪɢɠɢɜɥɟɧɢɟ [13]. ɗɬɨɬ ɧɟɞɨɫɬɚɬɨɤ ɨɬɧɨɫɢɬɫɹ ɝɥɚɜɧɵɦ ɨɛɪɚɡɨɦ ɤ ɩɨɩɵɬɤɚɦ ɪɚɫɲɢɪɢɬɶ ɩɭɥ ɩɪɨɝɟɧɢɬɨɪɧɵɯ ɤɥɟɬɨɤ ɢ, ɜ ɱɚɫɬɧɨɫɬɢ, ɤ ɬ.ɧ. «ɧɚɢɜɧɵɦ» ȽɋɄ.
ȼɚɠɧɟɣɲɚɹ ɯɚɪɚɤɬɟɪɢɫɬɢɤɚ ȽɋɄ – ɫɩɨɫɨɛɧɨɫɬɶ ɤ ɫɚɦɨɨɛɧɨɜɥɟɧɢɸ ɢ ɨɛɪɚɡɨɜɚɧɢɸ ɛɨɥɟɟ ɞɢɮɮɟɪɟɧɰɢɪɨɜɚɧɧɵɯ ɤɥɟɬɨɤ. ɇɟɫɦɨɬɪɹ ɧɚ
ɬɨ, ɱɬɨ ɞɨɫɬɭɩɧɵ ɦɟɬɨɞɵ ɨɛɧɚɪɭɠɟɧɢɹ ȽɋɄ in vitro, ɬɚɤɢɟ, ɤɚɤ ɤɨɥɨɧɢɟɨɛɪɚɡɭɸɳɢɟ ɤɥɟɬɤɢ ɫ ɜɵɫɨɤɢɦ ɩɪɨɥɢɮɟɪɚɬɢɜɧɵɦ ɩɨɬɟɧɰɢɚɥɨɦ
(HPP-CFC), ɤɥɟɬɤɢ, ɢɧɢɰɢɢɪɭɸɳɢɟ ɞɨɥɝɨɜɪɟɦɟɧɧɭɸ ɤɭɥɶɬɭɪɭ (LTCIC)
ɢ
ɤɥɟɬɤɢ,
ɮɨɪɦɢɪɭɸɳɢɟ
ɤɨɥɨɧɢɢ
ɫ
ɦɨɪɮɨɥɨɝɢɟɣ
ɬɢɩɚ
«cobblestone» (CAFC), ɞɨ ɫɢɯ ɩɨɪ ɧɟɹɫɧɨ, ɨɛɧɚɪɭɠɢɜɚɸɬ ɥɢ ɜɫɟ ɷɬɢ
ɦɟɬɨɞɵ ɢɦɟɧɧɨ ɞɨɥɝɨɠɢɜɭɳɢɟ ɪɟɩɨɩɭɥɢɪɭɸɳɢɟ ȽɋɄ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ. ɋɭɳɟɫɬɜɭɸɬ ɢ ɦɟɬɨɞɵ ɩɨɞɫɱɟɬɚ ɹɞɪɨɫɨɞɟɪɠɚɳɢɯ ɤɥɟɬɨɤ, ɝɪɚɧɭɥɨɰɢɬɨɜ-ɦɚɤɪɨɮɚɝɨɜɵɯ (CFU-GM), ɷɪɢɬɪɨɢɞɧɵɯ (BFU-E) ɢ ɦɭɥɶɬɢɩɨɬɟɧɬɧɵɯ (CFU-GEMM) ɩɪɨɝɟɧɢɬɨɪɧɵɯ ɤɥɟɬɨɤ [18, 19,38,39, 54, 59,
67, 90, 99, 101].
26
ɑɟɥɨɜɟɱɟɫɤɢɟ ȽɋɄ ɨɛɧɚɪɭɠɢɜɚɸɬɫɹ ɜ ɩɨɩɭɥɹɰɢɢ ɤɥɟɬɨɤ, ɷɤɫɩɪɟɫɫɢɪɭɸɳɢɯ ɜɵɫɨɤɢɟ ɭɪɨɜɧɢ ɚɧɬɢɝɟɧɚ CD34 ɩɪɢ ɨɬɫɭɬɫɬɜɢɢ ɚɧɬɢɝɟɧɚ CD38 (CD34+ and CD38–) [18]. Ʉɨɧɰɟɧɬɪɚɰɢɹ ȽɋɄ ɜ ɩɭɩɨɜɢɧɧɨɣ
ɤɪɨɜɢ, ɤɚɤ ɛɵɥɨ ɩɨɤɚɡɚɧɨ, ɜɵɲɟ, ɱɟɦ ɜ ɤɨɫɬɧɨɦ ɦɨɡɝɟ ɜɡɪɨɫɥɵɯ ɢɥɢ ɜ
ɰɢɬɨɤɢɧ-ɦɨɛɢɥɢɡɨɜɚɧɧɨɣ ɩɟɪɢɮɟɪɢɱɟɫɤɨɣ ɤɪɨɜɢ ɜɡɪɨɫɥɵɯ [18]. ɗɬɚ
ɩɨɜɵɲɟɧɧɚɹ ɜɫɬɪɟɱɚɟɦɨɫɬɶ ɢ, ɜɢɞɢɦɨ, ɩɨɜɵɲɟɧɧɨɟ ɤɨɥɢɱɟɫɬɜɨ ȽɋɄ
ɢɡ ɉɄ, ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɤɥɟɬɤɚɦɢ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ, ɤɨɪɪɟɥɢɪɭɟɬ ɫ ɩɨɜɵɲɟɧɧɨɣ ɜɫɬɪɟɱɚɟɦɨɫɬɶɸ ɢ ɩɪɨɥɢɮɟɪɚɬɢɜɧɨɣ ɫɩɨɫɨɛɧɨɫɬɶɸ ɝɟɦɚɬɨɩɨɷɬɢɱɟɫɤɢɯ ɩɪɨɝɟɧɢɬɨɪɧɵɯ ɤɥɟɬɨɤ (ɤɚɤ ɨɛɧɚɪɭɠɢɜɚɸɬ CFU-GM, BFUE, CFU-GEMM) ɜ ɉɄ. ȼɢɞɢɦɨ, ɜ ɷɬɨɦ ɢ ɫɨɫɬɨɢɬ ɩɪɢɱɢɧɚ, ɩɨɱɟɦɭ ɦɚɥɵɟ ɤɨɥɢɱɟɫɬɜɚ ɫɨɛɪɚɧɧɨɣ ɉɄ (50–200 ɦɥ) ɦɨɝɭɬ ɢɦɟɬɶ ɤɥɢɧɢɱɟɫɤɭɸ
ɡɧɚɱɢɦɨɫɬɶ, ɬɨɝɞɚ ɤɚɤ ɝɨɪɚɡɞɨ ɛɨɥɶɲɢɟ ɤɨɥɢɱɟɫɬɜɚ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɧɟɨɛɯɨɞɢɦɵ ɞɥɹ ɭɫɩɟɲɧɨɣ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ [18, 19,22,34, 38, 39, 54, 59,
67, 90, 99, 101].
ȼɵɫɨɤɚɹ ɩɥɚɫɬɢɱɧɨɫɬɶ ȽɋɄ ɢɡ ɉɄ ɛɵɥɚ ɩɪɨɞɟɦɨɧɫɬɪɢɪɨɜɚɧɚ ɩɪɢ
ɢɯ ɞɢɮɮɟɪɟɧɰɢɚɰɢɢ ɜ ɤɥɟɬɤɢ ɪɚɡɧɵɯ ɬɤɚɧɟɣ, ɜɤɥɸɱɚɹ ɬɤɚɧɢ ɋɋɋ, ɱɬɨ
ɹɜɥɹɟɬɫɹ ɭɤɚɡɚɧɢɟɦ ɧɚ ɩɟɪɫɩɟɤɬɢɜɵ ɢɯ ɬɟɪɚɩɜɬɢɱɟɫɤɨɝɨ ɢɫɩɨɥɶɡɨɜɚɧɢɹ.
1.3.4. ɉɪɨɬɟɨɦɢɤɚ ȽɋɄ
ȼ ɬɟɱɟɧɢɟ ɩɪɟɞɲɟɫɬɜɭɸɳɢɯ ɥɟɬ ɧɚɛɥɸɞɚɥɨɫɶ ɜɨɡɪɚɫɬɚɧɢɟ ɱɢɫɥɚ
ɢɫɫɥɟɞɨɜɚɧɢɣ ɋɄ ɫ ɩɨɦɨɳɶɸ ɦɟɬɨɞɨɜ ɩɪɨɬɟɨɦɢɤɢ. ȼ ɷɬɢɯ ɪɚɛɨɬɚɯ
ɛɵɥɚ ɩɨɞɬɜɟɪɠɞɟɧɚ ɩɨɥɟɡɧɨɫɬɶ 2D ɞɥɹ ɪɚɡɞɟɥɟɧɢɹ ɫɥɨɠɧɵɯ ɛɟɥɤɨɜɵɯ
ɫɦɟɫɟɣ ɢɡ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɪɚɡɧɨɝɨ ɬɢɩɚ. ȼ ɱɚɫɬɧɨɫɬɢ, ɫɨɜɦɟɫɬɧɨɟ
ɢɫɩɨɥɶɡɨɜɚɧɢɟ 2D ɢ MALDI ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɢ ɞɥɹ ɢɞɟɧɬɢɮɢɤɚɰɢɢ
ɢ ɯɚɪɚɤɬɟɪɢɫɬɢɤɢ ɛɟɥɤɨɜ ɪɚɡɧɵɯ ɋɄ ɩɪɟɞɨɫɬɚɜɢɥɨ ɡɧɚɱɢɬɟɥɶɧɵɟ ɦɚɫɫɢɜɵ ɢɧɮɨɪɦɚɰɢɢ ɨ ɦɨɥɟɤɭɥɹɪɧɵɯ ɦɟɯɚɧɢɡɦɚɯ ɪɟɝɭɥɹɰɢɢ ɋɄ. ɂ, ɱɬɨ
ɟɳɟ ɛɨɥɟɟ ɜɚɠɧɨ, ɷɬɢ ɪɚɛɨɬɵ ɩɨɡɜɨɥɢɥɢ ɭɬɨɱɧɢɬɶ ɩɪɢɪɨɞɭ ɜɧɭɬɪɟɧɧɢɯ
27
ɜɡɚɢɦɨɞɟɣɫɬɜɢɣ ɦɟɠɞɭ ɪɚɡɧɵɦɢ ɫɭɛɤɥɟɬɨɱɧɵɦɢ ɫɬɪɭɤɬɭɪɚɦɢ ɢ ɨɩɪɟɞɟɥɢɬɶ ɪɨɥɶ ɛɟɥɤɨɜ ɜ ɦɨɥɟɤɭɥɹɪɧɵɯ ɩɪɟɜɪɚɳɟɧɢɹɯ, ɢɦɟɸɳɢɯ ɛɢɨɥɨɝɢɱɟɫɤɭɸ ɡɧɚɱɢɦɨɫɬɶ.
ɋ ɩɨɦɨɳɶɸ ɩɪɨɬɟɨɦɢɤɢ ɜɨɡɦɨɠɧɨ ɤɚɤ ɢɡɭɱɟɧɢɟ ɨɞɧɨɣ ɤɥɟɬɨɱɧɨɣ
ɩɨɩɭɥɹɰɢɢ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɞɪɭɝɨɣ, ɬɚɤ ɢ ɨɞɧɨɣ ɢ ɬɨɣ ɠɟ ɩɨɩɭɥɹɰɢɢ ɜ
ɪɚɡɧɵɯ ɭɫɥɨɜɢɹɯ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɞɨɫɬɢɝɚɟɬɫɹ ɩɨɧɢɦɚɧɢɟ ɩɨɜɟɞɟɧɢɹ ɤɨɧɤɪɟɬɧɨɣ ɩɨɩɭɥɹɰɢɢ ɋɄ, ɱɬɨ ɩɪɨɥɢɜɚɟɬ ɫɜɟɬ ɧɚ
ɮɚɤɬɨɪɵ, ɜɨɜɥɟɱɟɧɧɵɟ ɜ ɤɨɧɬɪɨɥɶ ɷɬɢɯ ɭɧɢɤɚɥɶɧɵɯ ɤɥɟɬɨɤ ɢ ɨɩɪɟɞɟɥɟɧɢɟ ɢɯ ɛɢɨɥɨɝɢɱɟɫɤɨɣ ɪɨɥɢ.
ȼ 2006 ɝ. Sun ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ ɩɪɟɞɩɪɢɧɹɥ ɩɨɩɵɬɤɭ ɫ ɩɨɦɨɳɶɸ
ɩɪɨɬɟɨɦɢɤɢ ɨɯɚɪɚɤɬɟɪɢɡɨɜɚɬɶ ɩɪɨɥɢɮɟɪɚɰɢɸ ɢ ɨɫɬɟɨɝɟɧɧɵɣ ɩɨɬɟɧɰɢɚɥ ɦɟɡɟɧɯɢɦɚɥɶɧɵɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ (MCK) ɜɨ ɜɪɟɦɹ ɩɚɫɫɢɪɨɜɚɧɢɹ ɢ
ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɬɶ ɛɟɥɤɢ, ɤɨɬɨɪɵɟ ɩɨ-ɪɚɡɧɨɦɭ ɪɟɝɭɥɢɪɭɸɬɫɹ ɜ MCK
ɜɨ ɜɪɟɦɹ ɩɚɫɫɢɪɨɜɚɧɢɹ ɢ ɨɫɬɟɨɝɟɧɧɨɣ ɞɢɮɮɟɪɟɧɰɢɚɰɢɢ [82]. ɂɦ ɭɞɚɥɨɫɶ ɩɨɤɚɡɚɬɶ, ɱɬɨ ɩɪɨɥɢɮɟɪɚɰɢɹ ɢ ɨɫɬɟɨɝɟɧɧɚɹ ɫɩɨɫɨɛɧɨɫɬɶ MCK
ɫɧɢɠɚɟɬɫɹ ɜɨ ɜɪɟɦɹ ɩɚɫɫɢɪɨɜɚɧɢɹ [82]. ɇɟɫɤɨɥɶɤɨ ɛɟɥɤɨɜ, ɤɚɤ ɛɵɥɨ
ɨɛɧɚɪɭɠɟɧɨ, ɩɨ-ɪɚɡɧɨɦɭ ɪɟɝɭɥɢɪɭɸɬɫɹ ɜɨ ɜɪɟɦɹ ɩɚɫɫɢɪɨɜɚɧɢɹ, ɢ ɫɪɟɞɢ ɧɢɯ ɛɵɥɢ ɛɟɥɤɢ, ɫɜɹɡɚɧɧɵɟ ɫ ɤɥɟɬɨɱɧɨɣ ɩɪɨɥɢɮɟɪɚɰɢɟɣ, ɤɥɟɬɨɱɧɵɦ ɰɢɤɥɨɦ, ɦɨɪɮɨɥɨɝɢɱɟɫɤɢɦɢ ɢɡɦɟɧɟɧɢɹɦɢ, ɚɩɨɩɬɨɡɨɦ, ɩɪɢɱɟɦ
ɤɨɥɢɱɟɫɬɜɨ ɷɬɢɯ ɛɟɥɤɨɜ ɫɧɢɠɚɥɨɫɶ ɜɨ ɜɪɟɦɹ ɩɚɫɫɢɪɨɜɚɧɢɹ [82]. Ɋɟɡɭɥɶɬɚɬɵ ɷɬɢɯ ɪɚɛɨɬ ɭɤɚɡɵɜɚɸɬ ɧɚ ɬɨ, ɱɬɨ ɩɨ-ɪɚɡɧɨɦɭ ɪɟɝɭɥɢɪɭɟɦɵɟ
ɩɚɫɫɚɠ-ɫɩɟɰɢɮɢɱɧɵɟ ɛɟɥɤɢ ɦɨɝɭɬ ɢɝɪɚɬɶ ɨɩɪɟɞɟɥɟɧɧɭɸ ɪɨɥɶ ɜ ɫɧɢɠɟɧɢɢ ɩɨɬɟɧɰɢɚɥɚ ɨɫɬɟɨɝɟɧɧɨɣ ɞɢɮɮɟɪɟɧɰɢɚɰɢɢ ɩɪɢ ɩɚɫɫɢɪɨɜɚɧɢɢ.
Ȼɨɥɟɟ ɬɨɝɨ, ɩɪɨɥɢɮɟɪɚɰɢɨɧɧɵɣ ɢ ɨɫɬɟɨɝɟɧɧɵɣ ɩɨɬɟɧɰɢɚɥ MCK ɫɭɳɟɫɬɜɟɧɧɨ ɫɧɢɠɚɥɢɫɶ ɫ ɭɜɟɥɢɱɟɧɢɟɦ ɱɢɫɥɚ ɩɚɫɫɚɠɟɣ.
Ⱦɥɹ ɨɬɜɟɬɚ ɧɚ ɜɨɩɪɨɫ, ɨɬɜɟɬɫɬɜɟɧɧɚ ɥɢ ɡɚ ɫɧɢɠɟɧɢɟ ɩɪɨɥɢɮɟɪɚɰɢɨɧɧɨɝɨ ɢ ɨɫɬɟɨɝɟɧɧɨɝɨ ɩɨɬɟɧɰɢɚɥɚ ɩɪɢ ɩɚɫɫɢɪɨɜɚɧɢɢ ɷɤɫɩɪɟɫɫɢɹ
ɫɩɟɰɢɮɢɱɟɫɤɢɯ ɛɟɥɤɨɜ, ɷɬɢ ɢɫɫɥɟɞɨɜɚɬɟɥɢ ɢɫɩɨɥɶɡɨɜɚɥɢ ɤɥɚɫɫɢɱɟɫɤɢɣ
28
ɩɪɨɬɟɨɦɧɵɣ ɚɧɚɥɢɡ ɞɥɹ ɩɪɨɮɢɥɢɪɨɜɚɧɢɹ ɢɡɦɟɧɟɧɢɣ ɝɥɨɛɚɥɶɧɨɣ ɛɟɥɤɨɜɨɣ ɷɤɫɩɪɟɫɫɢɢ ɜ MCK ɩɪɢ ɩɚɫɫɢɪɨɜɚɧɢɢ ɢ ɨɫɬɟɨɝɟɧɧɨɣ ɞɢɮɮɟɪɟɧɰɢɚɰɢɢ [82]. ɂɡɦɟɧɟɧɢɹ ɛɟɥɤɨɜɨɝɨ ɩɪɨɮɢɥɹ ɛɵɥɢ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɵ
ɩɪɢ ɢɫɩɨɥɶɡɨɜɚɧɢɢ ɤɥɟɬɨɤ ɜ ɪɚɡɧɵɯ ɩɚɫɫɚɠɚɯ ɢɥɢ ɜ ɪɚɡɧɵɟ ɦɨɦɟɧɬɵ
ɨɫɬɟɨɝɟɧɧɨɣ ɞɢɮɮɟɪɟɧɰɢɚɰɢɢ. ȼɫɟɝɨ ɨɤɨɥɨ 100 ɧɨɪɦɚɥɢɡɨɜɚɧɧɵɯ
ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ, ɤɨɬɨɪɵɟ ɧɟ ɢɡɦɟɧɢɥɢɫɶ ɜ ɪɚɡɧɵɟ ɦɨɦɟɧɬɵ ɜɪɟɦɟɧɢ,
ɛɵɥɢ ɨɬɨɛɪɚɧɵ ɞɥɹ MALDI-ɚɧɚɥɢɡɚ ɞɥɹ ɨɛɟɫɩɟɱɟɧɢɹ ɤɨɧɬɪɨɥɹ (ɫɬɚɧɞɚɪɬɚ ɫɪɚɜɧɟɧɢɹ).
ɂɫɩɨɥɶɡɨɜɚɧɢɟ ɤɥɚɫɫɢɱɟɫɤɨɝɨ ɢɧɫɬɪɭɦɟɧɬɚɪɢɹ ɩɪɨɬɟɨɦɢɤɢ (2D ɢ
ɢɞɟɧɬɢɮɢɤɚɰɢɹ ɫ ɩɨɦɨɳɶɸ MALDI-ɫɩɟɤɬɪɨɫɤɨɩɢɢ) ɭɤɚɡɚɥɨ ɧɚ ɧɟɫɤɨɥɶɤɨ ɛɟɥɤɨɜ, ɤɨɬɨɪɵɟ, ɜɨɡɦɨɠɧɨ, ɩɪɢɱɚɫɬɧɵ ɩɪɹɦɨ ɢɥɢ ɤɨɫɜɟɧɧɨ ɤ
ɤɥɟɬɨɱɧɨɦɭ ɪɨɫɬɭ ɢ ɦɭɥɶɬɢɩɨɬɟɧɰɢɢ. ɋɨɡɞɚɧɢɟ 2D-ɪɟɮɟɪɟɧɫɧɨɣ ɤɚɪɬɵ ɛɭɞɟɬ ɫɩɨɫɨɛɫɬɜɨɜɚɬɶ ɨɛɧɚɪɭɠɟɧɢɸ ɤɨɥɢɱɟɫɬɜɟɧɧɵɯ ɢ ɤɚɱɟɫɬɜɟɧɧɵɯ ɢɡɦɟɧɟɧɢɣ ɜ ɛɟɥɤɨɜɨɣ ɷɤɫɩɪɟɫɫɢɢ ɜ ɨɬɜɟɬ ɧɚ ɫɟɪɢɚɥɶɧɨɟ ɫɭɛɤɭɥɶɬɢɜɢɪɨɜɚɧɢɟ ɢ ɨɫɬɟɨɝɟɧɧɭɸ ɞɢɮɮɟɪɟɧɰɢɚɰɢɸ MCK.
ȼ 2007 ɝ. Roubelakis ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ ɢɫɩɨɥɶɡɨɜɚɥ 2D ɢ MALDIɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɸ ɞɥɹ ɩɨɥɭɱɟɧɢɹ ɛɟɥɤɨɜɨɣ ɤɚɪɬɵ ɤɭɥɶɬɢɜɢɪɨɜɚɧɧɵɯ ɆɋɄ ɢɡ ɚɦɧɢɨɬɢɱɟɫɤɨɣ ɠɢɞɤɨɫɬɢ ɜɬɨɪɨɝɨ ɬɪɢɦɟɫɬɪɚ (Aɀ) ɢ
ɫɪɚɜɧɢɥ ɟɟ ɫ ɤɭɥɶɬɢɜɢɪɨɜɚɧɧɵɦɢ MɋɄ ɢɡ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ [74]. Ⱦɥɹ
261 ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɨɝɨ ɛɟɥɤɚ ɮɭɧɤɰɢɨɧɚɥɶɧɵɟ ɩɪɨɮɢɥɢ ɛɟɥɤɨɜ ɢɡ
ɞɜɭɯ ɷɬɢɯ ɢɫɬɨɱɧɢɤɨɜ ɛɵɥɢ ɚɧɚɥɨɝɢɱɧɵ. Ɉɞɧɚɤɨ, ɤɭɥɶɬɢɜɢɪɨɜɚɧɧɵɟ
Aɀ-ɆɋɄ ɨɛɧɚɪɭɠɢɥɢ ɧɟɫɤɨɥɶɤɨ ɭɧɢɤɚɥɶɧɵɯ ɛɟɥɤɨɜ, ɫɜɹɡɚɧɧɵɯ ɫ
ɩɪɨɥɢɮɟɪɚɰɢɟɣ ɢ ɩɪɢɦɢɬɢɜɧɵɦ ɮɟɧɨɬɢɩɨɦ, ɤɨɬɨɪɵɟ ɦɨɝɭɬ ɩɪɨɹɜɥɹɬɶ
ɱɟɬɤɢɟ ɫɜɨɣɫɬɜɚ ɞɜɭɯ ɬɢɩɨɜ ɤɥɟɬɨɤ. ɉɪɢɧɢɦɚɹ ɜɨ ɜɧɢɦɚɧɢɟ ɥɟɝɤɭɸ
ɞɨɫɬɭɩɧɨɫɬɶ ɷɬɨɝɨ ɧɨɜɨɝɨ ɢɫɬɨɱɧɢɤɚ ɤɥɟɬɨɤ ɢ ɜɨɡɦɨɠɧɨɫɬɶ ɪɚɡɦɧɨɠɟɧɢɹ ɆɋɄ ɞɥɹ ɢɫɫɥɟɞɨɜɚɧɢɹ ɋɄ, Aɀ ɹɜɥɹɟɬɫɹ ɨɬɥɢɱɧɵɦ ɩɨɫɬɚɜɳɢɤɨɦ
ɆɋɄ ɤɚɤ ɞɥɹ ɷɤɫɩɟɪɢɦɟɧɬɨɜ, ɬɚɤ ɢ ɞɥɹ ɬɟɪɚɩɢɢ [74]. ɉɪɢɦɟɪɨɦ ɛɟɥɤɚ,
ɨɛɧɚɪɭɠɟɧɧɨɝɨ ɜ ɤɭɥɶɬɢɜɢɪɨɜɚɧɧɵɯ Aɀ-ɆɋɄ ɢ ɆɋɄ ɢɡ ɤɨɫɬɧɨɝɨ
29
ɦɨɡɝɚ, ɹɜɥɹɟɬɫɹ ɜɢɦɟɧɬɢɧ, ɤɨɬɨɪɵɣ ɩɪɟɞɫɬɚɜɥɹɟɬ ɫɨɛɨɣ ɝɥɚɜɧɵɣ ɮɢɥɚɦɟɧɬɧɵɣ ɛɟɥɨɤ-ɢɧɬɟɪɦɟɞɢɚɬɨɪ ɜ ɆɋɄ ɢ ɱɚɫɬɨ ɢɫɩɨɥɶɡɭɟɬɫɹ ɤɚɤ
ɦɚɪɤɟɪ ɪɚɡɜɢɬɢɹ ɤɥɟɬɨɤ ɢ ɬɤɚɧɟɣ [41,69]. Ȼɵɥɨ ɬɚɤɠɟ ɩɨɤɚɡɚɧɨ, ɱɬɨ
ɜɢɦɟɧɬɢɧ ɭɱɚɫɬɜɭɟɬ ɜ ɪɹɞɟ ɤɪɢɬɢɱɟɫɤɢɯ ɞɟɣɫɬɜɢɣ, ɫɜɹɡɚɧɧɵɯ ɫ ɨɪɝɚɧɢɡɚɰɢɟɣ ɛɟɥɤɨɜ, ɤɨɬɨɪɵɟ ɜɨɜɥɟɱɟɧɵ ɜ ɚɞɝɟɡɢɸ ɢ ɪɟɝɭɥɢɪɭɸɬ ɮɭɧɤɰɢɢ ɢɧɬɟɝɪɢɧɚ, ɦɢɝɪɚɰɢɸ ɢ ɤɥɟɬɨɱɧɭɸ ɫɢɝɧɚɥɢɡɚɰɢɸ.
ȼ ɷɬɨɣ ɫɜɹɡɢ ɜɢɦɟɧɬɢɧ ɫɱɢɬɚɟɬɫɹ ɤɥɸɱɟɜɨɣ ɦɨɥɟɤɭɥɨɣ ɜ ɮɢɡɢɨɥɨɝɢɱɟɫɤɢɯ ɩɪɨɰɟɫɫɚɯ, ɬɚɤɢɯ, ɤɚɤ ɤɥɟɬɨɱɧɵɣ ɝɨɦɟɨɫɬɚɡ, ɚɩɨɩɬɨɡ, ɰɟɥɨɫɬɧɨɫɬɶ ɷɧɞɨɬɟɥɢɹ ɢ ɩɨɜɪɟɠɞɟɧɢɟ ɧɟɪɜɚ [41,69]. Ⱦɪɭɝɢɦ ɩɪɢɦɟɪɨɦ ɹɜɥɹɟɬɫɹ ɝɚɥɟɫɬɢɧ-1, ɜɚɠɧɚɹ ɦɨɥɟɤɭɥɚ ɪɟɝɭɥɹɰɢɢ ɋɄ, ɨɛɧɚɪɭɠɟɧɧɚɹ ɧɚ
ɤɥɟɬɨɱɧɨɣ ɩɨɜɟɪɯɧɨɫɬɢ ɆɋɄ [44], ɭɱɚɫɬɜɭɸɳɚɹ ɜ ɜɧɟɤɥɟɬɨɱɧɵɯ
ɜɡɚɢɦɨɞɟɣɫɬɜɢɹɯ ɦɚɬɪɢɤɫ-ɤɥɟɬɤɚ ɢ ɪɟɝɭɥɢɪɭɸɳɚɹ ɤɥɟɬɨɱɧɭɸ ɞɢɮɮɟɪɟɧɰɢɚɰɢɸ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ, ɩɪɨɥɢɮɟɪɚɰɢɸ ɢ ɚɩɨɩɬɨɡ ɡɚ ɫɱɟɬ ɜɡɚɢɦɨɞɟɣɫɬɜɢɹ ɫ ɜɧɟɤɥɟɬɨɱɧɵɦ ɦɚɬɪɢɤɫɨɦ ɢ ɢɦɦɭɧɧɨɣ ɫɢɫɬɟɦɨɣ [13,25].
Ɍɪɚɧɫɞɭɰɢɧ-ɩɨɞɨɛɧɵɣ ɛɟɥɨɤ-ɭɫɢɥɢɬɟɥɶ 3, ɨɛɧɚɪɭɠɟɧɧɵɣ ɜ ɤɭɥɶɬɢɜɢɪɨɜɚɧɧɵɯ ɆɋɄ ɢɡ ɨɛɨɢɯ ɢɫɬɨɱɧɢɤɨɜ, ɹɜɥɹɟɬɫɹ ɭɱɚɫɬɧɢɤɨɦ Wnt-ɩɭɬɢ
ɩɟɪɟɞɚɱɢ ɫɢɝɧɚɥɚ, ɜɥɢɹɸɳɟɝɨ ɧɚ ɪɨɫɬ ɢ ɪɚɡɜɢɬɢɟ ɢ, ɬɚɤɢɦ ɨɛɪɚɡɨɦ,
ɨɩɪɟɞɟɥɹɸɳɟɝɨ ɫɭɞɶɛɭ ɤɥɟɬɨɤ [21].
ȼ 2009 ɝ. Mareddy ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ [61] ɢɫɩɨɥɶɡɨɜɚɥ ɩɪɨɬɟɨɦɢɤɭ
ɞɥɹ ɢɡɭɱɟɧɢɹ ɦɨɥɟɤɭɥɹɪɧɵɯ ɦɟɯɚɧɢɡɦɨɜ, ɭɩɪɚɜɥɹɸɳɢɯ ɫɚɦɨɨɛɧɨɜɥɟɧɢɟɦ ɢ ɞɢɮɮɟɪɟɧɰɢɚɰɢɟɣ ɆɋɄ. ɐɟɥɶɸ ɷɬɨɝɨ ɢɫɫɥɟɞɨɜɚɧɢɹ ɛɵɥɨ ɫɨɡɞɚɧɢɟ ɩɨɥɧɨɣ ɩɪɨɬɟɨɦɧɨɣ ɪɟɮɟɪɟɧɫ-ɤɚɪɬɵ ɆɋɄ ɢɡ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ
(ɆɋɄ-ɄɆ), ɤɨɬɨɪɚɹ ɩɨɦɨɝɥɚ ɛɵ ɥɭɱɲɟ ɩɨɧɹɬɶ ɜɧɭɬɪɟɧɧɢɟ ɦɟɯɚɧɢɡɦɵ
ɫɚɦɨɨɛɧɨɜɥɟɧɢɹ ɢ ɞɢɮɮɟɪɟɧɰɢɚɰɢɢ ɆɋɄ-ɄɆ. Ȼɟɥɤɨɜɵɣ ɩɪɨɮɢɥɶ
ɤɥɨɧɚɥɶɧɵɯ ɩɨɩɭɥɹɰɢɣ ɆɋɄ ɛɵɥ ɢɡɭɱɟɧ ɫ ɩɨɦɨɳɶɸ ɞɜɭɦɟɪɧɨɣ ɠɢɞɤɨɫɬɧɨɣ
ɯɪɨɦɚɬɨɝɪɚɮɢɢ/MALDI-ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɢ
ɢ
ɫɢɫɬɟɦɵ
MASCOT (Matrix Science) ɞɥɹ ɞɟɤɨɧɜɨɥɸɬɧɨɣ ɨɛɪɚɛɨɬɤɢ ɦɚɫɫɫɩɟɤɬɪɨɜ ɢ ɩɨɥɭɱɟɧɢɹ ɜɟɪɨɹɬɧɨɫɬɧɵɯ ɯɚɪɚɤɬɟɪɢɫɬɢɤ ɞɥɹ ɤɚɠɞɨɝɨ ɢɡ
30
ɨɛɪɚɡɰɨɜ [61]. ȼɫɟɝɨ ɛɵɥɨ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɨ 83 ɛɟɥɤɚ, ɜɤɥɸɱɚɹ ɫɬɪɭɤɬɭɪɧɵɟ ɢ ɰɢɬɨɫɤɟɥɟɬɧɵɟ, ɤɚɥɶɰɢɣ-ɫɜɹɡɵɜɚɸɳɢɟ, ɰɢɬɨɤɢɧɟɬɢɱɟɫɤɢɟ, ɚ
ɬɚɤɠɟ ɩɪɟɞɫɬɚɜɢɬɟɥɟɣ ɫɟɦɟɣɫɬɜɚ ɮɢɥɚɦɟɧɬɨɜ-ɢɧɬɟɪɦɟɞɢɚɬɨɪɨɜ.
ȼ 2007 ɝ. Seshi ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ ɩɪɟɞɫɬɚɜɢɥ ɧɨɜɵɣ 2D ɩɪɨɬɨɤɨɥ, ɜ
ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɤɨɬɨɪɵɦ ɨɛɪɚɡɰɵ ɛɟɥɤɨɜ ɢɡ ɧɨɪɦɚɥɶɧɵɯ ɢ ɪɚɤɨɜɵɯ ɦɟɡɟɧɯɢɦɚɥɶɧɵɯ ɩɪɨɝɟɧɢɬɨɪɧɵɯ ɤɥɟɬɨɤ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɱɟɥɨɜɟɤɚ ɛɵɥɢ
ɢɫɩɨɥɶɡɨɜɚɧɵ ɤɚɤ ɦɨɞɟɥɶ ɞɥɹ ɧɨɜɨɣ ɤɨɦɛɢɧɚɰɢɢ ɠɢɞɤɨɮɚɡɧɨɝɨ ɢɡɨɷɥɟɤɬɪɢɱɟɫɤɨɝɨ ɮɨɤɭɫɢɪɨɜɚɧɢɹ (ɂɗɎ) ɫ 2D [78]. ɉɪɟɞɜɚɪɢɬɟɥɶɧɨɟ
ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɟ ɬɚɤɢɦ ɫɩɨɫɨɛɨɦ ɩɨɡɜɨɥɢɥɨ ɩɨɥɭɱɢɬɶ ɩɹɬɶ ɫɥɟɞɭɸɳɢɯ ɩɨɞɮɪɚɤɰɢɣ: ɮɪɚɤɰɢɹ 1 (pI 3,0–4,6), ɮɪɚɤɰɢɹ 2 (pI 4,6–5,4),
ɮɪɚɤɰɢɹ 3 (pI 5,4–6,2), ɮɪɚɤɰɢɹ 4 (pI 6,2–7,0), ɮɪɚɤɰɢɹ 5 (pI 7,0–10,0)
[67]. ɉɪɢ ɷɬɢɯ ɭɫɥɨɜɢɹɯ 2D ɜɵɹɜɢɥ 5000 ɛɟɥɨɤ-ɫɨɞɟɪɠɚɳɢɯ ɩɹɬɟɧ ɜ
ɞɢɚɩɚɡɨɧɟ ɪɇ 4,6–7,0. ɂɡɛɢɪɚɬɟɥɶɧɨɟ ɧɚɧɟɫɟɧɢɟ ɦɟɬɤɢ ɜ ɤɨɦɛɢɧɚɰɢɢ ɫ
ɩɨɫɥɟɞɭɸɳɢɦ MALDI ɩɨɡɜɨɥɢɥɨ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɬɶ ɛɟɥɤɢ, ɷɤɫɩɪɟɫɫɢɪɭɟɦɵɟ ɪɚɤɨɜɵɦɢ ɤɥɟɬɤɚɦɢ.
72 ɢɡ ɷɬɢɯ ɛɟɥɤɨɜ (56%) ɷɤɫɩɪɟɫɫɢɪɨɜɚɥɢɫɶ ɜ 1,25 ɪɚɡɚ ɚɤɬɢɜɧɟɟ
ɢɥɢ ɜ ɬɚɤɨɣ ɠɟ ɫɬɟɩɟɧɢ ɩɨɞɚɜɥɹɥɢɫɶ ɜ ɪɚɤɨɜɵɯ ɤɥɟɬɤɚɯ ɩɨ ɫɪɚɜɧɟɧɢɸ
ɫ ɧɨɪɦɚɥɶɧɵɦɢ. ɉɨɥɭɱɟɧɧɵɟ ɞɚɧɧɵɟ ɨɛɫɭɠɞɚɥɢɫɶ ɜ ɫɜɹɡɢ ɫ ɢɡɦɟɧɟɧɢɟɦ ɛɢɨɥɨɝɢɱɟɫɤɢɯ ɩɪɨɰɟɫɫɨɜ ɜ ɦɟɡɟɧɯɢɦɚɥɶɧɵɯ ɩɪɨɝɟɧɢɬɨɪɧɵɯ
ɤɥɟɬɤɚɯ, ɩɨɪɚɠɟɧɧɵɯ ɥɟɣɤɟɦɢɟɣ. ȼ ɱɚɫɬɧɨɫɬɢ, ɜɵɹɫɧɢɥɨɫɶ, ɱɬɨ ɪɹɞ
ɰɢɬɨɫɬɪɭɤɬɭɪɧɵɯ ɛɟɥɤɨɜ ɢɡɛɢɪɚɬɟɥɶɧɨ ɪɟɝɭɥɢɪɭɟɬɫɹ ɜ ɪɚɤɨɜɵɯ ɤɥɟɬɤɚɯ [78].
ɂɫɩɨɥɶɡɨɜɚɧɢɟ ɜɵɲɟɨɩɢɫɚɧɧɨɝɨ ɩɪɢɟɦɚ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɹ ɜɫɟ
ɱɚɳɟ ɧɚɛɥɸɞɚɟɬɫɹ ɜ ɩɪɨɬɟɨɦɢɤɟ, ɨɞɧɚɤɨ, ɧɟɫɦɨɬɪɹ ɧɚ ɟɝɨ ɜɵɫɨɤɭɸ
ɪɚɡɪɟɲɚɸɳɭɸ ɫɩɨɫɨɛɧɨɫɬɶ, ɧɟ ɫɬɚɥɨ ɲɢɪɨɤɨ ɪɚɫɩɪɨɫɬɪɚɧɟɧɧɵɦ.
Ɏɪɚɤɰɢɨɧɢɪɨɜɚɧɢɟ ɨɛɪɚɡɰɨɜ, ɤ ɬɨɦɭ ɠɟ, ɦɨɠɟɬ ɩɪɢɜɨɞɢɬɶ ɤ ɩɨɬɟɪɟ
ɛɟɥɤɨɜ ɢɥɢ ɪɚɡɞɟɥɟɧɢɸ ɤɚɤɨɝɨ-ɥɢɛɨ ɛɟɥɤɚ ɦɟɠɞɭ ɞɜɭɦɹ ɮɪɚɤɰɢɹɦɢ,
ɱɬɨ ɡɚɬɪɭɞɧɹɟɬ ɢɯ ɤɨɥɢɱɟɫɬɜɟɧɧɭɸ ɨɰɟɧɤɭ. ɗɬɨ ɨɝɪɚɧɢɱɟɧɢɟ ɨɫɨɛɟɧɧɨ
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ɭɦɟɫɬɧɨ ɩɪɢɧɹɬɶ ɜɨ ɜɧɢɦɚɧɢɟ ɩɪɢ ɫɪɚɜɧɢɬɟɥɶɧɵɯ ɢɫɫɥɟɞɨɜɚɧɢɹɯ ɛɟɥɤɨɜ. Ɍɟɦ ɧɟ ɦɟɧɟɟ, ɩɪɨɬɟɨɦɧɵɟ ɷɤɫɩɟɪɢɦɟɧɬɵ ɜ ɰɟɥɹɯ ɫɨɡɞɚɧɢɹ ɩɨɥɧɨɣ ɛɟɥɤɨɜɨɣ ɤɚɪɬɵ ɬɪɟɛɭɸɬ ɩɨɜɵɲɟɧɧɨɣ ɪɚɡɪɟɲɚɸɳɟɣ ɫɩɨɫɨɛɧɨɫɬɢ
ɦɟɬɨɞɨɜ ɞɚɠɟ ɫ ɭɱɟɬɨɦ ɭɤɚɡɚɧɧɵɯ ɧɟɞɨɫɬɚɬɤɨɜ.
ɉɨɩɵɬɤɢ ɨɰɟɧɢɬɶ ɩɪɨɬɟɨɦɢɤɭ ȽɋɄ ɢ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɩɪɨɝɟɧɢɬɨɪɧɵɯ ɤɥɟɬɨɤ (ȽɉɄ) ɞɨɥɠɧɵ ɞɨɩɨɥɧɹɬɶ ɪɟɡɭɥɶɬɚɬɵ ɢɫɫɥɟɞɨɜɚɧɢɣ
ɷɬɢɯ ɨɛɴɟɤɬɨɜ ɦɟɬɨɞɚɦɢ ɝɟɧɨɦɢɤɢ. Tao ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ ɢɫɩɨɥɶɡɨɜɚɥ
ɩɪɨɬɟɨɦɢɤɭ ɞɥɹ ɫɪɚɜɧɟɧɢɹ ɱɟɥɨɜɟɱɟɫɤɢɯ CD34+ ɤɥɟɬɨɤ ɢɡ ɩɭɩɨɜɢɧɧɨɣ
ɤɪɨɜɢ ɫɨ ɡɪɟɥɵɦɢ CD15+ ɦɢɟɥɨɢɞɧɵɦɢ ɤɥɟɬɤɚɦɢ [86]. Ȼɵɥɨ ɨɛɧɚɪɭɠɟɧɨ, ɱɬɨ CD34+ ɤɥɟɬɤɢ ɢɦɟɸɬ ɨɬɧɨɫɢɬɟɥɶɧɨ ɛɨɥɟɟ ɜɵɫɨɤɭɸ ɤɨɧɰɟɧɬɪɚɰɢɸ ɹɞɟɪɧɵɯ ɛɟɥɤɨɜ, ɱɟɦ ɡɪɟɥɵɟ ɤɥɟɬɤɢ. Ȼɟɥɤɢ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ ɢ
ɲɚɩɟɪɨɧɵ, ɚ ɬɚɤɠɟ ɛɟɥɤɢ, ɜɚɠɧɵɟ ɞɥɹ ɦɟɠɤɥɟɬɨɱɧɨɝɨ ɩɟɪɟɧɨɫɚ, ɞɨɦɢɧɢɪɨɜɚɥɢ ɜ CD34+ ɤɥɟɬɤɚɯ, ɚ ɧɟ ɜ CD15+ ɤɥɟɬɤɚɯ. 8 ɧɨɜɵɯ ɛɟɥɤɨɜ,
ɨɛɥɚɞɚɸɳɢɯ ɧɨɜɵɦɢ ɮɭɧɤɰɢɹɦɢ, ɬɚɤɠɟ ɛɵɥɨ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɨ.
Ɉɬɦɟɬɢɦ, ɱɬɨ ɩɪɢ ɚɧɚɥɢɡɟ ɢɧɮɨɪɦɚɰɢɢ, ɩɨɥɭɱɟɧɧɨɣ ɫ ɩɨɦɨɳɶɸ
ɝɟɧɨɦɢɤɢ ɢ ɩɪɨɬɟɨɦɢɤɢ ɧɚ ɤɥɟɬɤɚɯ ɱɟɥɨɜɟɤɚ, ɫɥɟɞɭɟɬ ɭɱɢɬɵɜɚɬɶ, ɱɬɨ
ɩɨɩɭɥɹɰɢɢ ɬɚɤɢɯ ɤɥɟɬɨɤ ɧɟ ɨɛɧɚɪɭɠɢɜɚɸɬ ɪɚɡɥɢɱɢɣ ɜ ɤɚɪɬɢɧɚɯ ɷɤɫɩɪɟɫɫɢɢ ɦɟɠɞɭ ȽɋɄ ɢ ȽɉɄ [86].
Ɍɨɥɶɤɨ ɦɟɧɶɲɢɧɫɬɜɨ CD34+ ɤɥɟɬɨɤ ɭɞɨɜɥɟɬɜɨɪɹɟɬ ɮɭɧɤɰɢɨɧɚɥɶɧɵɦ ɤɪɢɬɟɪɢɹɦ ȽɋɄ. Ⱦɚɠɟ ɩɨɩɭɥɹɰɢɹ CD34+CD38– ɤɥɟɬɨɤ ɜɤɥɸɱɚɟɬ
ɜ ɫɟɛɹ ɬɨɥɶɤɨ ɧɟɡɧɚɱɢɬɟɥɶɧɭɸ ɱɚɫɬɶ ɞɨɥɝɨɜɪɟɦɟɧɧɨ ɪɟɩɨɩɭɥɢɪɭɸɳɢɯ
ȽɋɄ ɢɡ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ [86]. ȿɫɥɢ ɦɵ ɯɨɬɢɦ ɥɭɱɲɟ ɪɚɫɩɨɡɧɚɜɚɬɶ ɮɟɧɨɬɢɩɵ ɤɥɟɬɨɤ ɱɟɥɨɜɟɤɚ ɞɥɹ ɪɚɡɝɪɚɧɢɱɟɧɢɹ ȽɋɄ ɢ ȽɉɄ, ɢɧɮɨɪɦɚɰɢɹ,
ɩɨɥɭɱɟɧɧɚɹ ɫ ɩɨɦɨɳɶɸ ɝɟɧɨɦɢɤɢ ɢ ɩɪɨɬɟɨɦɢɤɢ, ɛɭɞɟɬ ɤɪɚɣɧɟ ɧɟɨɛɯɨɞɢɦɚ. Ⱥ ɞɥɹ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɭɠɟ ɢɦɟɸɳɟɣɫɹ ɢɧɮɨɪɦɚɰɢɢ ɷɬɢɯ ɧɚɭɤ
ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟ ɝɟɧɵ ɢ ɛɟɥɤɢ ɞɨɥɠɧɵ ɛɵɬɶ ɩɪɨɬɟɫɬɢɪɨɜɚɧɵ ɜ
ɮɭɧɤɰɢɨɧɚɥɶɧɵɯ ɢɫɫɥɟɞɨɜɚɧɢɹɯ ȽɋɄ (ɧɚɩɪɢɦɟɪ, ɤɨɥɨɧɢɟɨɛɪɚɡɭɸɳɢɟ
ɟɞɢɧɢɰɵ ɜɵɫɨɤɨɝɨ ɩɪɨɥɢɮɟɪɚɬɢɜɧɨɝɨ ɩɨɬɟɧɰɢɚɥɚ – HPP-CFC) ɢ ȽɉɄ
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(ɫɨɞɟɪɠɚɧɢɟ ɜ ɤɪɨɜɢ ɧɚɢɛɨɥɟɟ ɩɪɢɦɢɬɢɜɧɵɯ ɩɪɟɞɲɟɫɬɜɟɧɧɢɤɨɜ ɝɟɦɨɩɨɷɡɚ LTC-IC – long-term culture-initiating cells ɢ ɤɥɟɬɨɤ, ɨɛɪɚɡɭɸɳɢɯ
ɨɛɥɚɫɬɢ ɛɭɥɵɠɧɢɤɚ – CAFC) [86].
ɂɡɭɱɟɧɢɟ ɩɨɜɵɲɟɧɧɨɣ ɢɥɢ ɫɧɢɠɟɧɧɨɣ ɷɤɫɩɪɟɫɫɢɢ ɩɪɨɞɭɤɰɢɢ
ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɯ ɝɟɧɨɜ ɩɪɨɞɨɥɠɚɟɬɫɹ ɜ ɪɹɞɟ ɥɚɛɨɪɚɬɨɪɢɣ ɢ
ɞɨɥɠɧɨ ɩɪɢɜɟɫɬɢ ɤ ɥɭɱɲɟɦɭ ɩɨɧɢɦɚɧɢɸ ɤɚɤ ɮɭɧɤɰɢɣ ɷɬɢɯ ɝɟɧɨɜ, ɬɚɤ
ɢ ɢɯ ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɯ ɩɪɨɞɭɤɬɨɜ.
ɉɨɫɥɟ ɭɬɨɱɧɟɧɢɹ ɮɭɧɤɰɢɣ ɷɬɢɯ ɷɤɫɩɪɟɫɫɢɪɭɸɳɢɯ ɝɟɧɨɜ, ɩɪɨɮɢɥɢɪɨɜɚɧɢɟ ɝɟɧɨɜ ɫɬɚɧɟɬ ɛɨɥɟɟ ɡɧɚɱɢɦɵɦ. ɉɨɥɧɨɟ ɤɚɪɬɢɪɨɜɚɧɢɟ ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɯ ɝɟɧɧɵɯ ɢ ɛɟɥɤɨɜɵɯ ɤɚɪɬ ɞɨɥɠɧɨ, ɜ ɫɜɨɸ ɨɱɟɪɟɞɶ, ɩɨɦɨɱɶ ɜ ɨɰɟɧɤɟ ɦɨɥɟɤɭɥɹɪɧɵɯ ɩɭɬɟɣ ɫɢɝɧɚɥɢɡɚɰɢɢ, ɚɫɫɨɰɢɢɪɨɜɚɧɧɵɯ
ɫ ɪɚɡɧɵɦɢ ɧɚɛɨɪɚɦɢ ɩɨɩɭɥɹɰɢɢ ȽɋɄ. Ⱦɨɩɨɥɧɹɬ ɷɬɢ ɢɫɫɥɟɞɨɜɚɧɢɹ
ɧɚɛɥɸɞɟɧɢɹ ɡɚ ɩɪɨɬɟɨɦɧɵɦɢ ɤɨɦɩɨɧɟɧɬɚɦɢ ɤɥɟɬɨɤ, ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɩɪɟɞɥɨɠɟɧɧɵɯ ɷɬɚɥɨɧɧɵɯ ɬɨɱɟɤ ɫɪɚɜɧɟɧɢɹ. Ⱦɥɹ ɭɫɤɨɪɟɧɢɹ ɬɚɤɢɯ ɪɚɛɨɬ ɜɚɠɧɨ ɢɦɟɬɶ ɧɟɤɭɸ ɫɬɚɪɬɨɜɭɸ ɩɥɚɬɮɨɪɦɭ, ɫ ɟɞɢɧɨɨɛɪɚɡɧɵɦɢ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɦɢ ɩɪɨɰɟɞɭɪɚɦɢ, ɨɛɳɟɩɪɢɧɹɬɵɦɢ ɧɚɭɱɧɵɦ
ɫɨɨɛɳɟɫɬɜɨɦ.
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2. ɆȺɌȿɊɂȺɅɕ ɂ ɆȿɌɈȾɕ
2.1. Ʉɥɟɬɨɱɧɵɟ ɥɢɧɢɢ
Ɉɫɬɟɨɫɚɪɤɨɦɚ ɱɟɥɨɜɟɤɚ ɤɥɟɬɨɱɧɨɣ ɥɢɧɢɢ MG63 ɛɵɥɚ ɢɫɩɨɥɶɡɨɜɚɧɚ
ɜ ɤɚɱɟɫɬɜɟ ɦɨɞɟɥɶɧɨɣ ɫɢɫɬɟɦɵ ɞɥɹ ɩɪɨɬɟɨɦɧɵɯ ɢɫɫɥɟɞɨɜɚɧɢɣ ɨɫɬɟɨɛɥɚɫɬɨɜ. Ⱥɤɬɢɜɢɪɨɜɚɧɧɚɹ ɮɥɭɨɪɟɫɰɟɧɰɢɟɣ ɫɨɪɬɢɪɨɜɤɚ ɤɥɟɬɨɤ (FACS) ɛɵɥɚ
ɢɫɩɨɥɶɡɨɜɚɧɚ ɞɥɹ ɤɨɧɬɪɨɥɹ ɫɨɞɟɪɠɚɧɢɹ ȾɇɄ ɫ ɰɟɥɶɸ ɨɩɪɟɞɟɥɟɧɢɹ ɫɬɟɩɟɧɢ G0/G1 ɫɢɧɯɪɨɧɢɡɚɰɢɢ ɜ ɤɥɟɬɨɱɧɨɣ ɩɨɩɭɥɹɰɢɢ. ɗɬɨ ɧɟɨɛɯɨɞɢɦɨ ɞɥɹ
ɩɨɞɬɜɟɪɠɞɟɧɢɹ ɬɨɝɨ, ɱɬɨ ɧɚɛɥɸɞɚɟɦɵɟ ɦɨɥɟɤɭɥɹɪɧɵɟ ɢɡɦɟɧɟɧɢɹ ɜɵɡɜɚɧɵ ɭɫɥɨɜɢɹɦɢ ɷɤɫɩɟɪɢɦɟɧɬɚ, ɚ ɧɟ ɪɚɡɥɢɱɢɹɦɢ ɦɟɠɞɭ ɤɥɟɬɤɚɦɢ, ɧɚɯɨɞɹɳɢɦɢɫɹ ɧɚ ɪɚɡɧɵɯ ɫɬɚɞɢɹɯ ɤɥɟɬɨɱɧɨɝɨ ɰɢɤɥɚ.
2.2. Ɇɨɧɨɧɭɤɥɟɚɪɧɵɟ ɤɥɟɬɤɢ
Ɇɨɧɨɧɭɤɥɟɚɪɧɵɟ ɤɥɟɬɤɢ ɜɵɞɟɥɹɥɢ ɦɟɬɨɞɚɦɢ ɝɪɚɞɢɟɧɬɧɨɝɨ ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɧɢɹ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ Ficoll-Paque ɩɥɨɬɧɨɫɬɶɸ d=1,077
ɝ/ɫɦ3, ɨɛɪɚɛɨɬɤɢ ɨɛɪɚɡɰɨɜ ɥɢɡɢɪɭɸɳɢɦ ɪɚɫɬɜɨɪɨɦ, ɫɨɫɬɨɹɳɟɝɨ ɢɡ
ɯɥɨɪɢɞɚ ɚɦɦɨɧɢɹ, ɝɢɞɪɨɤɚɪɛɨɧɚɬɚ ɤɚɥɢɹ ɢ ɧɚɬɪɢɟɜɨɣ ɫɨɥɢ ɷɬɢɥɟɧɞɢɚɦɢɧɭɤɫɭɫɧɨɣ ɤɢɫɥɨɬɵ ɜ ɫɨɨɬɧɨɲɟɧɢɢ 1:9 ɢ ɫɟɞɢɦɟɧɬɚɰɢɢ ɤɥɟɬɨɤ ɜ 3%
ɪɚɫɬɜɨɪɟ ɠɟɥɚɬɢɧɚ ɩɭɬɟɦ ɧɚɫɥɚɢɜɚɧɢɹ ɝɟɩɚɪɢɧɢɡɢɪɨɜɚɧɧɵɯ ɨɛɪɚɡɰɨɜ
ɜ ɫɨɨɬɧɨɲɟɧɢɢ 1:3.
2.3. Ƚɟɦɨɩɨɷɬɢɱɟɫɤɢɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ (ȽɋɄ)
ɂɫɩɨɥɶɡɨɜɚɧɧɵɟ ɜ ɨɩɵɬɚɯ ȽɋɄ ɛɵɥɢ ɥɸɛɟɡɧɨ ɩɪɟɞɨɫɬɚɜɥɟɧɵ
ɛɚɧɤɨɦ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ (London Cord Blood Bank, Deansbrook Road,
Edgeware HA8 9BD). Ɋɚɡɦɧɨɠɟɧɢɟ ȽɋɄ ɨɫɭɳɟɫɬɜɥɹɥɢ in vitro.
Ⱦɥɹ ɜɵɞɟɥɟɧɢɹ ɢ ɨɱɢɫɬɤɢ ȽɋɄ (ɪɢɫ. 2.1) ɩɪɢɦɟɧɹɥɢ ɩɪɨɰɟɞɭɪɭ
ɪɚɡɞɟɥɟɧɢɹ ɫɭɫɩɟɧɡɢɢ ɤɥɟɬɨɤ ɜ ɝɪɚɞɢɟɧɬɚɯ ɮɢɤɨɥɥɚ (Ficoll-Paque,
Pharmacia). ɉɟɪɜɵɦ ɲɚɝɨɦ ɜɵɞɟɥɟɧɢɹ ȽɋɄ ɹɜɥɹɟɬɫɹ ɜɧɟɫɟɧɢɟ 20 ɦɥ
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ɤɥɟɬɨɱɧɨɣ ɫɭɫɩɟɧɡɢɢ ɜ ɪɨɫɬɨɜɭɸ ɫɪɟɞɭ IMDM ɢ 2% ɎȻɋ ɜ 50 ɦɥ ɰɟɧɬɪɢɮɭɠɧɭɸ ɩɪɨɛɢɪɤɭ. Ɂɚɬɟɦ 10 ɦɥ Ficoll-Paque (FP) ɧɚɫɥɚɢɜɚɥɢɫɶ
ɩɨɞ ɨɛɪɚɡɟɰ ɤɥɟɬɨɤ. Ɋɚɡɞɟɥɟɧɢɟ ɨɛɪɚɡɰɚ ɞɨɫɬɢɝɚɥɨɫɶ ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɧɢɟɦ (400g) ɜ ɬɟɱɟɧɢɟ 35 ɦɢɧ ɩɪɢ 20°C.
Ɉɬɬɚɢɜɚɧɢɟ
ɉɨɞɫɱɟɬ ɤɥɟɬɨɤ
Ɋɚɡɞɟɥɟɧɢɟ
ɜ Ficoll-Paque
Ʉɭɥɶɬɢɜɢɪɨɜɚɧɢɟ
ɉɨɞɫɱɟɬ ɤɥɟɬɨɤ
ȼɵɞɟɥɟɧɢɟ CD34+ ɫ ɩɨɦɨɳɶɸ ɦɚɝɧɢɬɧɵɯ ɫɮɟɪ
ɉɨɞɫɱɟɬ ɤɥɟɬɨɤ
ɉɪɨɬɨɱɧɚɹ
ɰɢɬɨɦɟɬɪɢɹ
ɐɢɬɨɫɩɢɧ
Ɉɤɪɚɲɢɜɚɧɢɟ
ɩɨ Wright
Ʉɭɥɶɬɢɜɢɪɨɜɚɧɢɟ
ɉɪɨɬɟɨɦɧɵɣ ɚɧɚɥɢɡ
(∼2×106 ɤɥɟɬɨɤ)
Ʉɭɥɶɬɢɜɢɪɨɜɚɧɢɟ
ɂɦɦɭɧɨɝɢɫɬɨɥɨɝɢɱɟɫɤɨɟ
ɨɤɪɚɲɢɜɚɧɢɟ
Ɋɢɫ. 2.1. Ɍɢɩɢɱɧɚɹ ɛɥɨɤ-ɫɯɟɦɚ ɨɱɢɫɬɤɢ, ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ ɢ ɜɵɞɟɥɟɧɢɹ
ȽɋɄ
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ɉɪɢ ɢɫɩɨɥɶɡɨɜɚɧɢɢ ɫɬɟɪɢɥɶɧɨɣ ɩɥɚɫɬɢɤɨɜɨɣ ɩɢɩɟɬɤɢ ɫɟɪɟɞɢɧɧɵɣ
ɫɥɨɣ (ɥɢɦɮɨɰɢɬɵ) ɩɟɪɟɧɨɫɢɥɫɹ ɜ ɱɢɫɬɭɸ ɰɟɧɬɪɢɮɭɠɧɭɸ ɩɪɨɛɢɪɤɭ. ɇɚ
ɫɥɟɞɭɸɳɟɦ ɷɬɚɩɟ ɤ ɥɢɦɮɨɰɢɬɚɦ ɜ ɩɪɨɛɢɪɤɟ ɞɨɛɚɜɥɹɥɨɫɶ 10 ɦɥ PBS.
Ʉɥɟɬɤɢ ɫɭɫɩɟɧɞɢɪɨɜɚɥɢ ɚɤɤɭɪɚɬɧɵɦ ɜɫɚɫɵɜɚɧɢɟɦ ɢ ɜɵɩɭɫɤɚɧɢɟɦ ɢɡ
ɩɢɩɟɬɤɢ, ɡɚɬɟɦ ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɥɢ (200g) ɜ ɬɟɱɟɧɢɟ 10 ɦɢɧ ɩɪɢ 20°C.
ɋɭɩɟɪɧɚɬɚɧɬ ɫɥɢɜɚɥɢ ɢ ɫɭɫɩɟɧɞɢɪɨɜɚɥɢ ɥɢɦɮɨɰɢɬɵ ɜ 10 ɦɥ PBS ɜɫɚɫɵɜɚɧɢɟɦ ɢ ɜɵɩɭɫɤɚɧɢɟɦ ɢɡ ɩɢɩɟɬɤɢ. Ɂɚɬɟɦ ɨɛɪɚɡɟɰ ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɥɢ (200g) ɜ ɬɟɱɟɧɢɟ 10 ɦɢɧ ɩɪɢ 20°C ɢ ɩɨɞɜɟɪɝɚɥɢ ɨɱɢɫɬɤɟ.
2.4. ȼɵɞɟɥɟɧɢɟ CD34+ ɫ ɩɨɦɨɳɶɸ ɦɚɝɧɢɬɧɵɯ ɫɮɟɪ
ɉɪɨɰɟɞɭɪɚ ɜɤɥɸɱɚɟɬ ɜ ɫɟɛɹ ɪɟɫɭɫɩɟɧɞɢɪɨɜɚɧɢɟ ɤɥɟɬɨɱɧɨɝɨ ɫɝɭɫɬɤɚ ɜ 300 ɦɤɥ ɛɭɮɟɪɚ (ɧɚ 108 ɤɥɟɬɨɤ). ɋɥɟɞɭɸɳɚɹ ɫɬɚɞɢɹ – ɞɨɛɚɜɥɟɧɢɟ
100 ɦɤɥ FcR ɛɥɨɤɢɪɭɸɳɟɝɨ ɪɟɚɝɟɧɬɚ ɧɚ 108 ɤɥɟɬɨɤ, ɩɟɪɟɦɟɲɢɜɚɧɢɟ ɢ
ɞɨɛɚɜɥɟɧɢɟ 100 ɦɤɥ ɝɚɩɬɟɧ-ɚɧɬɢɬɟɥ ɧɚ 108 ɤɥɟɬɨɤ, ɫɦɟɲɢɜɚɧɢɟ ɢ ɢɧɤɭɛɢɪɨɜɚɧɢɟ ɜ ɬɟɱɟɧɢɟ 15 ɦɢɧ ɩɪɢ 4°C ɞɥɹ ɞɨɫɬɢɠɟɧɢɹ ɨɩɬɢɦɚɥɶɧɨɝɨ
ɫɥɢɩɚɧɢɹ. Ʉɨɧɟɱɧɵɣ ɨɛɴɟɦ ɞɥɹ ɦɟɬɤɢ ɫɨɫɬɚɜɥɹɟɬ 500 ɦɤɥ ɧɚ 108 ɤɥɟɬɨɤ.
Ɂɚɬɟɦ ɤɥɟɬɤɢ ɬɳɚɬɟɥɶɧɨ ɩɪɨɦɵɜɚɸɬ ɛɭɮɟɪɨɦ, ɞɨɛɚɜɥɹɹ 10–20 ɪɚɡ ɨɤɪɚɲɢɜɚɸɳɢɣ ɨɛɴɟɦ (5–10 ɦɥ ɧɚ 108 ɤɥɟɬɨɤ), ɰɟɧɬɪɢɮɭɝɢɪɭɸɬ ɢ ɩɨɥɧɨɫɬɶɸ ɫɥɢɜɚɸɬ ɫɭɩɟɪɧɚɬɚɧɬ, ɡɚɬɟɦ ɪɟɫɭɫɩɟɧɞɢɪɭɸɬ ɫɝɭɫɬɨɤ ɨɫɬɨɪɨɠɧɨ,
ɞɨɛɚɜɥɹɹ ɛɭɮɟɪ ɞɨ ɤɨɧɟɱɧɨɝɨ ɨɛɴɟɦɚ 400 ɦɤɥ ɧɚ 108 ɤɥɟɬɨɤ. Ɂɚɬɟɦ ɞɨɛɚɜɥɹɸɬ 100 ɦɤɥ ɚɧɬɢɝɚɩɬɟɧɨɜɵɯ ɦɢɤɪɨɫɮɟɪ ɧɚ 108 ɤɥɟɬɨɤ (ɤɨɧɟɱɧɵɣ
ɦɟɬɹɳɢɣ ɨɛɴɟɦ ɫɨɫɬɚɜɥɹɟɬ 500 ɦɤɥ ɧɚ 108 ɤɥɟɬɨɤ), ɬɳɚɬɟɥɶɧɨ ɩɟɪɟɦɟɲɢɜɚɸɬ ɢ ɢɧɤɭɛɢɪɭɸɬ 15 ɦɢɧ ɩɪɢ ɬɟɦɩɟɪɚɬɭɪɟ 4°C. Ʉɥɟɬɤɢ ɡɚɬɟɦ ɨɬɦɵɜɚɸɬ ɢ ɪɟɫɭɫɩɟɧɞɢɪɭɸɬ, ɫ ɤɥɟɬɨɱɧɵɦ ɫɝɭɫɬɤɨɦ, ɢɧɤɭɛɢɪɭɟɦɵɦ ɜ
500 ɦɤɥ ɛɭɮɟɪɚ ɧɚ 108 ɤɥɟɬɨɤ. Ʉɨɥɨɧɤɚ ɞɥɹ ɦɚɝɧɢɬɧɨɣ ɫɟɩɚɪɚɰɢɢ ɨɩɪɟɞɟɥɹɟɬɫɹ ɭɫɥɨɜɢɹɦɢ ɷɤɫɩɟɪɢɦɟɧɬɚ. Ⱦɥɹ ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɢ ɤɨɥɨɧɤɚ
ɡɚɩɨɥɧɹɟɬɫɹ ɢ ɩɪɨɦɵɜɚɟɬɫɹ 500 ɦɤɥ ɛɭɮɟɪɚ, ɤɥɟɬɤɢ ɩɪɨɩɭɫɤɚɸɬɫɹ ɱɟɪɟɡ
ɮɢɥɶɬɪ (ɫ ɦɟɲ 30 ɦɤɥ, ɧɟɣɥɨɧ), ɫ ɭɞɚɥɟɧɢɟɦ ɫɝɭɫɬɤɨɜ, ɮɢɥɶɬɪ ɫɦɚɱɢɜɚ-
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ɟɬɫɹ ɛɭɮɟɪɨɦ ɩɟɪɟɞ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ. Ɂɚɬɟɦ ɤɥɟɬɤɢ ɧɚɧɨɫɹɬɫɹ ɧɚ ɤɨɥɨɧɤɭ, ɩɪɨɩɭɫɤɚɸɬɫɹ ɱɟɪɟɡ ɧɟɟ ɞɥɹ ɪɚɡɞɟɥɟɧɢɹ ɢ ɩɪɨɦɵɜɚɸɬɫɹ ɛɭɮɟɪɨɦ
3×500 ɦɤɥ, ɤɨɥɨɧɤɚ ɫɧɢɦɚɟɬɫɹ ɫ ɫɟɩɚɪɚɬɨɪɚ, ɩɨɦɟɳɚɟɬɫɹ ɜ ɩɨɞɯɨɞɹɳɭɸ
ɩɪɨɛɢɪɤɭ, ɧɚ ɤɨɥɨɧɤɭ ɧɚɧɨɫɢɬɫɹ 1 ɦɥ ɛɭɮɟɪɚ ɢ ɷɥɸɢɪɭɸɬɫɹ ɡɚɞɟɪɠɚɧɧɵɟ ɤɥɟɬɤɢ ɩɪɢ ɢɫɩɨɥɶɡɨɜɚɧɢɢ ɩɥɭɧɠɟɪɚ, ɱɬɨ ɦɢɧɢɦɢɡɢɪɭɟɬ ɤɨɥɢɱɟɫɬɜɨ ɤɥɟɬɨɤ, ɩɨɬɟɪɹɧɧɵɯ ɧɚ ɮɢɥɶɬɪɟ. ɗɬɚ ɫɬɚɞɢɹ ɩɨɜɬɨɪɹɟɬɫɹ ɧɚɧɟɫɟɧɢɟɦ
ɷɥɸɢɪɨɜɚɧɧɵɯ ɤɥɟɬɨɤ ɧɚ ɧɨɜɭɸ ɤɨɥɨɧɤɭ ɞɥɹ ɦɟɧɟɟ ɱɟɦ 107 CD34+ ɤɥɟɬɨɤ, ɡɚɬɟɦ ɫɦɵɜɚɸɬɫɹ ɢ ɷɥɸɢɪɭɸɬɫɹ ɛɭɮɟɪɨɦ ɡɚɞɟɪɠɚɧɧɵɟ ɤɥɟɬɤɢ.
Ⱦɥɹ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ ɜɵɞɟɥɟɧɧɵɯ ȽɋɄ ɢɫɩɨɥɶɡɨɜɚɥɢ ɩɢɬɚɬɟɥɶɧɵɟ
ɫɪɟɞɵ RPMI 1640 (Sigma), L-15 (Sigma), DɆȿɆ/F12 (Sigma) ɢ ɉɋɉ, ɫɨɞɟɪɠɚɳɢɟ 10% ɮɟɬɚɥɶɧɨɣ ɫɵɜɨɪɨɬɤɢ ɩɥɨɞɚ ɤɨɪɨɜɵ. Ʉɥɟɬɤɢ ɜɵɫɟɜɚɥɢ ɜ
ɤɭɥɶɬɭɪɚɥɶɧɵɟ 24 ɥɭɧɨɱɧɵɟ ɩɥɚɲɤɢ. Ʉɭɥɶɬɢɜɢɪɨɜɚɧɢɟ ɩɪɨɜɨɞɢɥɢ ɩɪɢ
37°ɋ ɜ ɭɜɥɚɠɧɟɧɧɨɣ ɚɬɦɨɫɮɟɪɟ ɫɨɞɟɪɠɚɳɟɣ 5%ɋɈ2. Ⱦɜɭɯɧɟɞɟɥɶɧɚɹ
ɩɪɨɰɟɞɭɪɚ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ ɋɄ ɢɡ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ ɞɚɧɚ ɜ ɬɚɛɥ. 2.1.
Ɍɚɛɥɢɰɚ 2.1. ɋɯɟɦɚ ɷɤɫɩɟɪɢɦɟɧɬɚ ɞɥɹ ɢɫɫɥɟɞɨɜɚɧɢɹ ȽɋɄ ɩɪɢ ɞɜɭɯɧɟɞɟɥɶɧɨɦ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɢ
Ⱦɧɢ Ɋɚɡɞɟɥɟɧɢɟ ɜ ȼɵɞɟɥɟɧɢɟ CD34+ Ʉɭɥɶɬɢɜɢ- ɉɪɨɬɨɱɧɚɹ ɉɨɞɫɱɟɬ ɐɢɬɨ- ɉɪɨɬɟɨɦFicoll-Paque ɫ ɩɨɦɨɳɶɸ ɦɚɝ- ɪɨɜɚɧɢɟ ɰɢɬɨɦɟɬɪɢɹ ɤɥɟɬɨɤ ɫɩɢɧ ɧɵɣ ɚɧɚɥɢɡ
ɧɢɬɧɵɯ ɫɮɟɪ
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ɉɨɫɟɜ
Ȼɚɡɨɜɵɣ
ɭɪɨɜɟɧɶ
Ɂɚɦɟɧɚ
ɫɪɟɞɵ
Ɂɚɦɟɧɚ
ɫɪɟɞɵ
Ɂɚɦɟɧɚ
ɫɪɟɞɵ
Ɂɚɦɟɧɚ
ɫɪɟɞɵ
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2.5. Ʉɥɟɬɤɢ ɢɡ ɢɧɬɢɦɵ (ɦɟɞɢɢ) ɚɨɪɬɵ
Ɇɚɬɟɪɢɚɥ ɞɥɹ ɢɫɫɥɟɞɨɜɚɧɢɹ ɩɨɥɭɱɚɥɢ ɢɡ ɚɭɬɨɩɫɢɣɧɵɯ ɨɛɪɚɡɰɨɜ
ɝɪɭɞɧɨɝɨ ɨɬɞɟɥɚ ɚɨɪɬ ɦɭɠɱɢɧ ɢ ɠɟɧɳɢɧ ɜ ɜɨɡɪɚɫɬɟ 40–65 ɥɟɬ ɜ ɬɟɱɟɧɢɟ 1,5–3 ɱɚɫɨɜ ɩɨɫɥɟ ɜɧɟɡɚɩɧɨɣ ɫɦɟɪɬɢ. ɉɪɢɱɢɧɨɣ ɫɦɟɪɬɢ ɜ ɩɨɞɚɜɥɹɸɳɟɦ ɛɨɥɶɲɢɧɫɬɜɟ ɫɥɭɱɚɟɜ ɛɵɥɚ ɨɫɬɪɚɹ ɫɟɪɞɟɱɧɨɫɨɫɭɞɢɫɬɚɹ ɧɟɞɨɫɬɚɬɨɱɧɨɫɬɶ. Ɉɛɪɚɛɨɬɤɭ ɚɭɬɨɩɫɢɣɧɨɝɨ ɦɚɬɟɪɢɚɥɚ ɩɪɨɜɨɞɢɥɢ ɜ ɫɬɟɪɢɥɶɧɵɯ ɭɫɥɨɜɢɹɯ. ɉɨɫɥɟ ɦɟɯɚɧɢɱɟɫɤɨɝɨ ɭɞɚɥɟɧɢɹ ɚɞɜɟɧɬɢɰɢɢ ɚɨɪɬɭ ɪɚɫɫɟɤɚɥɢ ɜɞɨɥɶ ɢ ɩɪɨɦɵɜɚɥɢ ɜ ɯɨɥɨɞɧɨɦ ɮɨɫɮɚɬɧɨɦ ɛɭɮɟɪɟ ɞɥɹ ɭɞɚɥɟɧɢɹ ɥɸɛɵɯ ɫɥɟɞɨɜ ɤɪɨɜɢ. ɂɡ ɥɨɫɤɭɬɚ ɚɨɪɬɵ ɜɵɪɟɡɚɥɢ ɭɱɚɫɬɤɢ, ɧɟ ɩɨɪɚɠɟɧɧɵɟ ɚɬɟɪɨɫɤɥɟɪɨɡɨɦ, ɚ ɬɚɤɠɟ ɭɱɚɫɬɤɢ, ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɟ ɪɚɡɥɢɱɧɵɦ ɜɢɞɚɦ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɩɨɪɚɠɟɧɢɣ (ɠɢɪɨɜɚɹ ɢɧɮɢɥɶɬɪɚɰɢɹ,
ɠɢɪɨɜɚɹ ɩɨɥɨɫɚ, ɥɢɩɨɮɢɛɪɨɡɧɚɹ ɛɥɹɲɤɚ, ɮɢɛɪɨɡɧɚɹ ɛɥɹɲɤɚ), ɜ ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɤɥɚɫɫɢɮɢɤɚɰɢɟɣ Stary [80].
ɉɪɢ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɬɢɩɚ ɩɨɪɚɠɟɧɢɹ ɪɭɤɨɜɨɞɫɬɜɨɜɚɥɢɫɶ ɫɥɟɞɭɸɳɢɦɢ ɩɪɟɞɫɬɚɜɥɟɧɢɹɦɢ. ȼɧɟɲɧɟ ɧɟɩɨɪɚɠɟɧɧɵɟ ɭɱɚɫɬɤɢ ɚɨɪɬ ɢ
ɭɱɚɫɬɤɢ ɫ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɦɢ ɩɨɪɚɠɟɧɢɹɦɢ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɥɢ
ɦɚɤɪɨɫɤɨɩɢɱɟɫɤɢ, ɚ ɡɚɬɟɦ ɦɢɤɪɨɫɤɨɩɢɱɟɫɤɢ ɜ ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɤɥɚɫɫɢɮɢɤɚɰɢɟɣ ɋɨɜɟɬɚ ɩɨ ɚɬɟɪɨɫɤɥɟɪɨɡɭ Ⱥɦɟɪɢɤɚɧɫɤɨɝɨ Ɉɛɳɟɫɬɜɚ ɩɨ ɢɡɭɱɟɧɢɸ ɫɟɪɞɰɚ.
ɍɱɚɫɬɤɢ ɢɧɬɢɦɵ ɫ ɧɚɱɚɥɶɧɵɦɢ ɩɨɪɚɠɟɧɢɹɦɢ (I ɬɢɩ ɩɨɪɚɠɟɧɢɹ)
ɦɚɤɪɨɫɤɨɩɢɱɟɫɤɢ ɩɪɟɞɫɬɚɜɥɹɥɢ ɫɨɛɨɣ ɭɱɚɫɬɤɢ ɫ ɝɥɚɞɤɨɣ ɠɟɥɬɨɜɚɬɨɣ
ɩɨɜɟɪɯɧɨɫɬɶɸ, ɢɧɨɝɞɚ ɫ ɦɟɥɤɢɦɢ ɠɟɥɬɵɦɢ ɬɨɱɤɚɦɢ. Ɇɢɤɪɨɫɤɨɩɢɱɟɫɤɢɟ ɢɡɦɟɧɟɧɢɹ ɛɵɥɢ ɦɢɧɢɦɚɥɶɧɵ. ɇɚɛɥɸɞɚɥɢɫɶ ɧɟɛɨɥɶɲɢɟ ɧɚɤɨɩɥɟɧɢɹ ɜɧɟɤɥɟɬɨɱɧɵɯ ɥɢɩɢɞɧɵɯ ɤɚɩɟɥɶ ɜ ɫɨɟɞɢɧɢɬɟɥɶɧɨ-ɬɤɚɧɧɨɦ ɦɚɬɪɢɤɫɟ. ɉɨɦɢɦɨ ɨɫɟɞɥɵɯ ɤɥɟɬɨɤ ɜ ɭɱɚɫɬɤɚɯ ɧɚɱɚɥɶɧɵɯ ɩɨɪɚɠɟɧɢɣ
ɦɨɠɧɨ ɛɵɥɨ ɨɛɧɚɪɭɠɢɬɶ ɭɜɟɥɢɱɟɧɧɨɟ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɜɧɟɲɧɟ ɧɟɢɡ-
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ɦɟɧɟɧɧɨɣ ɢɧɬɢɦɨɣ ɤɨɥɢɱɟɫɬɜɨ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɤɥɟɬɨɤ. ɇɢɤɚɤɢɯ ɧɚɪɭɲɟɧɢɣ ɜ ɫɬɪɭɤɬɭɪɟ ɬɤɚɧɢ ɧɟ ɜɵɹɜɥɹɥɨɫɶ.
ɀɢɪɨɜɵɟ ɩɨɥɨɫɵ (ɩɨɪɚɠɟɧɢɹ II ɬɢɩɚ) ɦɚɤɪɨɫɤɨɩɢɱɟɫɤɢ ɩɪɟɞɫɬɚɜɥɹɥɢ ɫɨɛɨɣ ɩɨɥɨɫɤɢ ɢ ɬɨɱɤɢ ɠɟɥɬɨɝɨ ɰɜɟɬɚ, ɧɟɦɧɨɝɨ ɜɵɫɬɭɩɚɸɳɢɟ ɧɚɞ ɩɨɜɟɪɯɧɨɫɬɶɸ ɫɨɫɭɞɚ. ɑɚɫɬɨ ɦɨɠɧɨ ɛɵɥɨ ɨɛɧɚɪɭɠɢɬɶ ɠɢɪɨɜɵɟ ɩɨɥɨɫɤɢ, ɫɥɢɜɲɢɟɫɹ ɦɟɠɞɭ ɫɨɛɨɣ ɜ ɛɨɥɟɟ ɤɪɭɩɧɵɟ ɫɬɪɭɤɬɭɪɵ
(ɤɥɚɫɬɟɪɵ). ɇɚ ɫɪɟɡɚɯ ɬɤɚɧɢ ɥɢɩɢɞɵ ɜɵɹɜɥɹɥɢɫɶ ɜ ɨɫɧɨɜɧɨɦ ɜɧɭɬɪɢɤɥɟɬɨɱɧɨ. ȼ ɫɨɟɞɢɧɢɬɟɥɶɧɨ-ɬɤɚɧɧɨɦ ɦɚɬɪɢɤɫɟ ɨɛɧɚɪɭɠɢɜɚɥɢɫɶ ɬɚɤɠɟ
ɜɧɟɤɥɟɬɨɱɧɵɟ ɥɢɩɢɞɵ. ɂɧɨɝɞɚ ɜ ɠɢɪɨɜɵɯ ɩɨɥɨɫɚɯ ɧɚɛɥɸɞɚɥɨɫɶ
ɨɛɢɥɶɧɨɟ ɪɚɡɪɚɫɬɚɧɢɟ ɜɧɟɤɥɟɬɨɱɧɨɝɨ ɦɚɬɪɢɤɫɚ.
Ʌɢɩɨɮɢɛɪɨɡɧɵɟ ɛɥɹɲɤɢ (ɩɨɪɚɠɟɧɢɹ Va ɬɢɩɚ). ɉɪɢ ɦɚɤɪɨɫɤɨɩɢɱɟɫɤɨɦ ɢɡɭɱɟɧɢɢ ɥɢɩɨɮɢɛɪɨɡɧɵɟ ɛɥɹɲɤɢ ɜɵɝɥɹɞɟɥɢ ɤɚɤ ɫɢɥɶɧɨ ɜɵɫɬɭɩɚɸɳɢɟ ɧɚɞ ɥɸɦɢɧɚɥɶɧɨɣ ɩɨɜɟɪɯɧɨɫɬɶɸ ɠɟɥɬɨɜɚɬɵɟ ɢɥɢ ɩɟɪɥɚɦɭɬɪɨɜɵɟ, ɤɪɭɝɥɵɟ ɢɥɢ ɷɥɥɢɩɫɨɢɞɧɵɟ ɨɛɪɚɡɨɜɚɧɢɹ. Ɇɢɤɪɨɫɤɨɩɢɱɟɫɤɢ
ɜ ɷɬɢɯ ɩɨɪɚɠɟɧɢɹɯ ɨɛɧɚɪɭɠɢɜɚɥɢɫɶ ɜɫɟ ɢɡɦɟɧɟɧɢɹ, ɯɚɪɚɤɬɟɪɧɵɟ ɞɥɹ
ɠɢɪɨɜɵɯ ɩɨɥɨɫ: ɧɚɤɨɩɥɟɧɢɟ ɜɧɭɬɪɢɤɥɟɬɨɱɧɵɯ ɥɢɩɢɞɨɜ, ɪɚɡɪɚɫɬɚɧɢɟ
ɜɧɟɤɥɟɬɨɱɧɨɝɨ ɦɚɬɪɢɤɫɚ. Ʉɪɨɦɟ ɷɬɨɝɨ, ɜ ɥɢɩɨɮɢɛɪɨɡɧɵɯ ɛɥɹɲɤɚɯ ɜɵɹɜɥɹɥɨɫɶ ɦɚɫɫɢɜɧɨɟ ɧɟɤɪɨɬɢɱɟɫɤɨɟ ɹɞɪɨ ɢ ɪɚɫɩɨɥɨɠɟɧɧɚɹ ɧɚɞ ɧɢɦ ɫɨɟɞɢɧɢɬɟɥɶɧɨ-ɬɤɚɧɧɚɹ ɩɨɤɪɵɲɤɚ. ȼ ɥɢɩɨɮɢɛɪɨɡɧɵɯ ɛɥɹɲɤɚɯ ɢɦɟɥɢɫɶ
ɭɱɚɫɬɤɢ, ɩɨ ɦɨɪɮɨɥɨɝɢɢ ɩɨɯɨɠɢɟ ɧɚ ɭɱɚɫɬɤɢ ɠɢɪɨɜɵɯ ɩɨɪɚɠɟɧɢɣ –
ɩɥɟɱɢ ɥɢɩɨɮɢɛɪɨɡɧɵɯ ɛɥɹɲɟɤ.
Ɏɢɛɪɨɡɧɵɟ ɛɥɹɲɤɢ (ɩɨɪɚɠɟɧɢɹ Vc ɬɢɩɚ). Ɏɢɛɪɨɡɧɵɟ ɛɥɹɲɤɢ
ɦɚɤɪɨɫɤɨɩɢɱɟɫɤɢ ɩɪɟɞɫɬɚɜɥɹɥɢ ɫɨɛɨɣ ɫɢɥɶɧɨ ɩɪɢɩɨɞɧɹɬɵɟ ɠɟɦɱɭɠɧɨɝɨ ɰɜɟɬɚ ɨɤɪɭɝɥɵɟ ɢɥɢ ɨɜɚɥɶɧɵɟ ɨɛɪɚɡɨɜɚɧɢɹ, ɦɢɤɪɨɫɤɨɩɢɱɟɫɤɢ ɫɨɫɬɨɹɳɢɟ ɜ ɨɫɧɨɜɧɨɦ ɢɡ ɝɪɭɛɨɝɨ ɫɨɟɞɢɧɢɬɟɥɶɧɨ-ɬɤɚɧɧɨɝɨ ɦɚɬɪɢɤɫɚ, ɫ
«ɡɚɦɭɪɨɜɚɧɧɵɦɢ» ɜ ɧɟɦ ɤɥɟɬɤɚɦɢ. Ʌɢɩɢɞɧɵɣ ɤɨɦɩɨɧɟɧɬ ɛɵɥ ɦɢɧɢɦɚɥɶɧɵɦ ɢɥɢ ɨɬɫɭɬɫɬɜɨɜɚɥ.
40
Ɂɚɬɟɦ ɫ ɩɨɦɨɳɶɸ ɩɢɧɰɟɬɨɜ ɢɧɬɢɦɭ ɨɬɞɟɥɹɥɢ ɨɬ ɦɟɞɢɢ, ɩɪɢ ɷɬɨɦ
ɪɚɡɞɟɥɟɧɢɟ ɫɥɨɟɜ ɩɪɨɢɫɯɨɞɢɥɨ ɩɨ ɜɧɭɬɪɟɧɧɟɣ ɩɨɝɪɚɧɢɱɧɨɣ ɷɥɚɫɬɢɱɟɫɤɨɣ ɦɟɦɛɪɚɧɟ. ȼɵɞɟɥɟɧɧɵɟ ɨɛɪɚɡɰɵ ɪɚɡɦɟɪɨɦ 1×1 ɫɦ ɜɧɨɜɶ ɬɳɚɬɟɥɶɧɨ ɩɪɨɦɵɜɚɥɢ ɜ ɯɨɥɨɞɧɨɦ ɮɨɫɮɚɬɧɨɦ ɛɭɮɟɪɟ, ɧɟɦɟɞɥɟɧɧɨ ɡɚɦɨɪɚɠɢɜɚɥɢ ɜ ɠɢɞɤɨɦ ɚɡɨɬɟ ɢ ɪɚɫɬɢɪɚɥɢ ɮɚɪɮɨɪɨɜɵɦ ɩɟɫɬɢɤɨɦ ɜ ɮɚɪɮɨɪɨɜɨɣ
ɫɬɭɩɤɟ ɞɨ ɩɨɪɨɲɤɨɨɛɪɚɡɧɨɝɨ ɫɨɫɬɨɹɧɢɹ. ɉɨɫɥɟ ɭɩɚɪɢɜɚɧɢɹ ɠɢɞɤɨɝɨ
ɚɡɨɬɚ ɩɪɢ ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ ɨɛɪɚɡɰɵ ɥɢɨɮɢɥɢɡɢɪɨɜɚɥɢ ɜ ɥɢɨɮɢɥɶɧɨɣ ɫɭɲɤɟ ɜ ɬɟɱɟɧɢɟ 6 ɱɚɫɨɜ. ɏɪɚɧɟɧɢɟ ɨɛɪɚɡɰɨɜ ɜɩɥɨɬɶ ɞɨ ɜɵɞɟɥɟɧɢɹ ɛɟɥɤɨɜ ɩɪɨɜɨɞɢɥɢ ɩɪɢ –80°ɋ ɜ ɧɢɡɤɨɬɟɦɩɟɪɚɬɭɪɧɨɦ ɦɨɪɨɡɢɥɶɧɢɤɟ. Ɂɚɦɨɪɨɠɟɧɧɵɟ ɨɛɪɚɡɰɵ ɩɨɞɜɟɪɝɚɥɢ ɢɡɦɟɥɶɱɟɧɢɸ ɜ ɚɬɦɨɫɮɟɪɟ
ɠɢɞɤɨɝɨ ɚɡɨɬɚ, ɢɡɛɟɝɚɹ ɨɬɬɚɢɜɚɧɢɹ. ɉɨɥɭɱɟɧɧɵɣ ɩɨɪɨɲɨɤ ɪɚɫɬɜɨɪɹɥɢ
(ɫɭɫɩɟɧɞɢɪɨɜɚɥɢ) ɜ ɛɭɮɟɪɧɨɦ ɪɚɫɬɜɨɪɟ ɦɨɱɟɜɢɧɵ ɜ ɫɨɨɬɧɨɲɟɧɢɢ 1 ɝ
ɩɨɪɨɲɤɚ ɧɚ 7 ɦɥ ɛɭɮɟɪɚ ɩɪɢ ɩɨɫɬɨɹɧɧɨɦ ɜɫɬɪɹɯɢɜɚɧɢɢ ɩɪɢ ɤɨɦɧɚɬɧɨɣ
ɬɟɦɩɟɪɚɬɭɪɟ. ɋɭɫɩɟɧɡɢɸ ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɥɢ ɩɪɢ 15000 g ɜ ɬɟɱɟɧɢɟ 30
ɦɢɧ ɩɪɢ ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ. Ɋɚɡɞɟɥɟɧɧɵɟ ɮɪɚɤɰɢɢ ɯɪɚɧɢɥɢ ɩɪɢ –
80°C. ɉɟɪɟɞ ɩɪɨɜɟɞɟɧɢɟɦ ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɞɨɛɚɜɥɹɥɢ ɢɧɝɢɛɢɬɨɪ ɩɪɨɬɟɚɡ.
Ⱦɥɹ ɜɵɞɟɥɟɧɢɹ ɛɟɥɤɨɜ ɢɡ ɩɨɪɨɲɤɨɨɛɪɚɡɧɵɯ ɨɛɪɚɡɰɨɜ ɢɫɩɨɥɶɡɨɜɚɥɢ ɞɜɚ ɦɟɬɨɞɚ. ȼ ɩɟɪɜɨɦ ɦɟɬɨɞɟ ɩɨɪɨɲɨɤ ɪɚɫɬɜɨɪɹɥɢ ɜ ɦɨɱɟɜɢɧɧɨɦ
ɛɭɮɟɪɟ pH=8,0 (ɦɨɱɟɜɢɧɚ 8 Ɇ, ɬɢɨɦɨɱɟɜɢɧɚ 2 Ɇ, CHAPS 4%, ɞɢɬɢɨɬɪɟɢɬɨɥ 1%, Ɍɪɢɫ 20 ɦɆ) ɢɡ ɪɚɫɱɟɬɚ 7 ɦɥ ɛɭɮɟɪɚ ɧɚ 1 ɝ ɩɨɪɨɲɤɚ. Ȼɭɮɟɪ
ɝɨɬɨɜɢɥɢ ɡɚɪɚɧɟɟ, ɮɢɥɶɬɪɨɜɚɥɢ ɱɟɪɟɡ ɮɢɥɶɬɪ ɫ ɞɢɚɦɟɬɪɨɦ ɩɨɪ
0,22 ɦɤɦ ɢ ɯɪɚɧɢɥɢ ɞɨ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɜ ɚɥɢɤɜɨɬɚɯ ɩɪɢ –80°ɋ. ɇɟɩɨɫɪɟɞɫɬɜɟɧɧɨ ɩɟɪɟɞ ɞɨɛɚɜɥɟɧɢɟɦ ɛɭɮɟɪɚ ɤ ɨɛɪɚɡɰɭ ɤ ɧɟɦɭ ɞɨɛɚɜɥɹɥɢ
ɤɨɤɬɟɣɥɶ ɢɡ ɢɧɝɢɛɢɬɨɪɨɜ ɩɪɨɬɟɚɡ (ɢɡ ɪɚɫɱɟɬɚ 1 ɦɤɥ/ɦɥ ɪɚɫɬɜɨɪɚ ɨɪɬɨɜɚɧɚɞɚɬɚ ɧɚɬɪɢɹ 1 Ɇ, 1 ɦɤɥ/ɦɥ ɪɚɫɬɜɨɪɚ ɚɩɪɨɬɢɧɢɧɚ 10 ɦɝ/ɦɥ,
2 ɦɤɥ/ɦɥ ɪɚɫɬɜɨɪɚ ɮɟɧɢɥɦɟɬɢɥɫɭɥɶɮɨɧɢɥɮɥɸɨɪɢɞɚ 0,5 Ɇ, 2 ɦɤɥ/ɦɥ
ɪɚɫɬɜɨɪɚ
ɥɟɭɩɟɩɬɢɧɚ
1 ɦɝ/ɦɥ,
2 ɦɤɥ/ɦɥ
ɪɚɫɬɜɨɪɚ
ɛɟɧɡɚɦɢɞɢɧɚ
100 ɦɆ). ɗɤɫɬɪɚɤɰɢɸ ɛɟɥɤɨɜ ɩɪɨɜɨɞɢɥɢ ɜ ɬɟɱɟɧɢɟ 1 ɱɚɫɚ ɩɪɢ ɧɟɩɪɟ41
ɪɵɜɧɨɦ ɩɟɪɟɦɟɲɢɜɚɧɢɢ ɧɚ ɲɟɣɤɟɪɟ ɩɪɢ ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ. ɉɨ
ɨɤɨɧɱɚɧɢɢ ɷɤɫɬɪɚɤɰɢɢ ɨɛɪɚɡɰɵ ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɥɢ ɩɪɢ 15000 g ɩɪɢ
ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ ɜ ɬɟɱɟɧɢɟ 30 ɦɢɧɭɬ, ɨɬɛɢɪɚɥɢ ɫɭɩɟɪɧɚɬɚɧɬ ɢ
ɯɪɚɧɢɥɢ ɩɪɢ –80°ɋ ɞɨ ɩɪɨɜɟɞɟɧɢɹ 2D ɷɥɟɤɬɪɨɮɨɪɟɡɚ.
ȼɨ ɜɬɨɪɨɦ ɦɟɬɨɞɟ ɩɨɪɨɲɨɤ ɪɚɫɬɜɨɪɹɥɢ ɜ ɥɟɞɹɧɨɦ Ripa-ɛɭɮɟɪɟ
pH=8,0 (Ɍɪɢɫ 50 ɦɆ, ɧɚɬɪɢɹ ɯɥɨɪɢɞ 150 ɦɆ, Ɍɪɢɬɨɧ X-100 1%, ɞɟɡɨɤɫɢɯɨɥɚɬ ɧɚɬɪɢɹ 1%, ɞɨɞɟɰɢɥɫɭɥɶɮɚɬ ɧɚɬɪɢɹ 0,1%). ɇɟɩɨɫɪɟɞɫɬɜɟɧɧɨ
ɩɟɪɟɞ ɞɨɛɚɜɥɟɧɢɟɦ ɛɭɮɟɪɚ ɤ ɨɛɪɚɡɰɭ ɤ ɧɟɦɭ ɞɨɛɚɜɥɹɥɢ ɜɵɲɟɨɩɢɫɚɧɧɵɣ ɤɨɤɬɟɣɥɶ ɢɡ ɢɧɝɢɛɢɬɨɪɨɜ ɩɪɨɬɟɚɡ. Ƚɨɦɨɝɟɧɢɡɚɰɢɸ ɨɛɪɚɡɰɨɜ ɜ ɛɭɮɟɪɟ ɜɵɩɨɥɧɹɥɢ ɧɚ ɝɨɦɨɝɟɧɢɡɚɬɨɪɟ ɬɤɚɧɟɣ Tissue Tearor (Biospec
Products, ɋɒȺ) ɩɪɢ 5–10000 ɨɛ./ɦɢɧ. 3 ɪɚɡɚ ɩɨ 10 ɫɟɤɭɧɞ ɫ ɩɨɫɥɟɞɭɸɳɟɣ ɦɹɝɤɨɣ ɫɨɧɢɮɢɤɚɰɢɟɣ ɩɪɢ 30% ɦɚɤɫɢɦɚɥɶɧɨɣ ɦɨɳɧɨɫɬɢ 3
ɪɚɡɚ ɩɨ 10 ɫ; ɨɩɟɪɚɰɢɢ ɜɵɩɨɥɧɹɥɢ ɧɚ ɥɶɞɭ. ɉɨ ɨɤɨɧɱɚɧɢɢ ɝɨɦɨɝɟɧɢɡɚɰɢɢ ɨɛɪɚɡɰɵ ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɥɢ ɩɪɢ 15000 g ɩɪɢ ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ 4°ɋ ɜ ɬɟɱɟɧɢɟ 30 ɦɢɧ., ɨɬɛɢɪɚɥɢ ɫɭɩɟɪɧɚɬɚɧɬ ɢ ɯɪɚɧɢɥɢ ɩɪɢ –
80°ɋ ɞɨ ɩɪɨɜɟɞɟɧɢɹ 2D ɷɥɟɤɬɪɨɮɨɪɟɡɚ.
Ʉɨɧɰɟɧɬɪɚɰɢɸ ɛɟɥɤɚ ɜ ɷɤɫɬɪɚɤɬɚɯ ɨɩɪɟɞɟɥɹɥɢ ɩɨ Lowry.
2.6. ɉɪɢɝɨɬɨɜɥɟɧɢɟ ɢ ɨɩɬɢɦɢɡɚɰɢɹ ɨɛɪɚɡɰɨɜ ɞɥɹ ɢɫɫɥɟɞɨɜɚɧɢɹ
Ⱦɥɹ ɜɵɞɟɥɟɧɢɹ ɛɟɥɤɨɜ ɢɡ ɤɥɟɬɨɤ ɢɫɩɨɥɶɡɨɜɚɥɨɫɶ ɪɚɡɪɭɲɟɧɢɟ ɤɥɟɬɨɱɧɵɯ ɦɟɦɛɪɚɧ ɫ ɩɨɦɨɳɶɸ ɨɛɪɚɛɨɬɤɢ ɭɥɶɬɪɚɡɜɭɤɨɦ. Ⱦɥɹ ɭɫɩɟɲɧɵɯ
ɢɫɫɥɟɞɨɜɚɧɢɣ ɩɪɨɬɟɨɦɚ ɢɫɤɥɸɱɢɬɟɥɶɧɨ ɜɚɠɧɵɦ ɹɜɥɹɟɬɫɹ ɷɮɮɟɤɬɢɜɧɨɟ ɪɚɡɞɟɥɟɧɢɟ ɫɥɨɠɧɵɯ ɛɟɥɤɨɜɵɯ ɫɦɟɫɟɣ, ɩɨɡɜɨɥɹɸɳɟɟ ɜ ɞɚɥɶɧɟɣɲɟɦ ɩɪɨɜɨɞɢɬɶ ɚɧɚɥɢɡ ɛɟɥɤɨɜ, ɩɪɢɫɭɬɫɬɜɭɸɳɢɯ ɜ ɧɢɡɤɢɯ ɤɨɧɰɟɧɬɪɚɰɢɹɯ. ȼ ɫɜɹɡɢ ɫɨ ɫɥɨɠɧɨɫɬɶɸ ɰɟɥɵɯ ɩɪɨɬɟɨɦɨɜ ɢ ɪɚɡɧɨɨɛɪɚɡɢɟɦ ɛɟɥɤɨɜɵɯ ɫɜɨɣɫɬɜ, ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ ɩɨɥɟɡɧɵɦ ɩɪɢɝɨɬɨɜɥɟɧɢɟ ɫɬɚɧɞɚɪɬɢɡɢɪɨɜɚɧɧɵɯ ɱɚɫɬɢɱɧɵɯ ɩɪɨɬɟɨɦɨɜ ɞɥɹ ɦɚɤɫɢɦɢɡɚɰɢɢ ɨɛɡɨɪɚ ɢ ɩɨɜɵɲɟɧɢɹ ɜɟɪɨɹɬɧɨɫɬɢ ɜɢɡɭɚɥɢɡɚɰɢɢ ɦɢɧɨɪɧɵɯ ɛɟɥɤɨɜ.
42
Ⱦɢɮɮɟɪɟɧɰɢɚɥɶɧɨɟ ɷɤɫɬɪɚɝɢɪɨɜɚɧɢɟ ɛɟɥɤɨɜ ɜ ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɢɯ ɫɭɛɤɥɟɬɨɱɧɨɣ ɥɨɤɚɥɢɡɚɰɢɟɣ ɨɫɭɳɟɫɬɜɥɹɥɢ ɫ ɩɨɦɨɳɶɸ ɤɨɦɦɟɪɱɟɫɤɢ ɞɨɫɬɭɩɧɨɝɨ ɧɚɛɨɪɚ ɪɟɚɝɟɧɬɨɜ ProteoExtract® Subcellular Proteome Extraction Kit
(S-PEK, Calbiochem, Germany). ɗɬɨɬ ɧɚɛɨɪ ɫɨɞɟɪɠɢɬ ɷɤɫɬɪɚɤɰɢɨɧɧɵɟ ɛɭɮɟɪɧɵɟ ɪɚɫɬɜɨɪɵ, ɩɪɢɝɨɬɨɜɥɟɧɧɵɟ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɫɨɟɞɢɧɟɧɢɣ ɜɵɫɨɤɨɣ ɱɢɫɬɨɬɵ, ɫɦɟɫɶ ɢɧɝɢɛɢɬɨɪɨɜ ɩɪɨɬɟɚɡ, ɩɪɟɞɨɬɜɪɚɳɚɸɳɢɯ ɪɚɡɪɭɲɟɧɢɟ
ɛɟɥɤɨɜ, ɢ ɧɭɤɥɟɚɡɭ (Benzonase®), ɭɫɬɪɚɧɹɸɳɭɸ ɡɚɝɪɹɡɧɹɸɳɢɟ ɧɭɤɥɟɢɧɨɜɵɟ ɤɢɫɥɨɬɵ. Ɉɞɧɢɦ ɢɡ ɩɪɟɢɦɭɳɟɫɬɜ S-PEK ɹɜɥɹɟɬɫɹ ɜɨɡɦɨɠɧɨɫɬɶ ɢɡɛɢɪɚɬɟɥɶɧɨɝɨ ɢ ɦɹɝɤɨɝɨ, ɫɨɯɪɚɧɹɸɳɟɝɨ ɫɬɪɭɤɬɭɪɧɭɸ ɰɟɥɨɫɬɧɨɫɬɶ, ɷɤɫɬɪɚɝɢɪɨɜɚɧɢɹ ɤɨɦɩɨɧɟɧɬɨɜ ɫɭɛɤɥɟɬɨɱɧɵɯ ɫɬɪɭɤɬɭɪ ɫɩɟɰɢɚɥɶɧɵɦɢ ɫɦɟɫɹɦɢ
ɪɟɚɝɟɧɬɨɜ. Ⱦɥɹ ɤɥɟɬɨɤ, ɜɵɪɚɳɟɧɧɵɯ ɜ ɫɭɫɩɟɧɡɢɢ, S-PEK ɧɚɱɢɧɚɟɬɫɹ ɫ
ɦɹɝɤɨɝɨ ɨɫɚɠɞɟɧɢɹ ɢ ɩɪɨɦɵɜɚɧɢɹ ɤɥɟɬɨɤ. Ⱦɥɹ ɡɚɦɨɪɨɠɟɧɧɵɯ ɤɥɟɬɨɤ ɢ
ɫɟɝɦɟɧɬɢɪɨɜɚɧɧɵɯ ɬɤɚɧɟɣ ɷɤɫɬɪɚɝɢɪɨɜɚɧɢɟ ɧɚɱɢɧɚɟɬɫɹ ɫ ɪɟɫɭɫɩɟɧɞɢɪɨɜɚɧɢɹ ɜ ɩɟɪɜɨɦ ɷɤɫɬɪɚɝɢɪɭɸɳɟɦ ɛɭɮɟɪɟ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɰɟɥɵɣ ɩɪɨɬɟɨɦ
ɩɪɟɜɪɚɳɚɟɬɫɹ ɜ ɫɭɛɩɪɨɬɟɨɦɵ ɦɟɧɶɲɟɣ ɫɥɨɠɧɨɫɬɢ ɜ ɨɬɧɨɲɟɧɢɢ ɫɜɨɟɝɨ
ɫɨɫɬɚɜɚ. ɉɨɷɬɚɩɧɨɟ ɩɪɢɦɟɧɟɧɢɟ ɬɪɟɯ ɛɭɮɟɪɧɵɯ ɫɦɟɫɟɣ ɩɨɡɜɨɥɹɟɬ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨ ɜɵɞɟɥɢɬɶ ɬɪɢ ɮɪɚɤɰɢɢ ɛɟɥɤɨɜ ɫ ɪɚɫɬɜɨɪɢɦɨɫɬɶɸ, ɢɡɦɟɧɹɸɳɟɣɫɹ ɨɬ ɦɚɤɫɢɦɚɥɶɧɨɣ ɤ ɦɢɧɢɦɚɥɶɧɨɣ.
ɉɟɪɜɨɣ ɫɬɚɞɢɟɣ ɩɟɪɟɞ ɷɤɫɬɪɚɝɢɪɨɜɚɧɢɟɦ ɹɜɥɹɟɬɫɹ ɩɟɪɟɦɟɲɢɜɚɧɢɟ
ɛɭɮɟɪɨɜ ɩɭɬɟɦ ɜɫɬɪɹɯɢɜɚɧɢɹ. ɉɪɨɰɟɞɭɪɚ ɧɚɱɢɧɚɟɬɫɹ ɫ ɨɫɬɨɪɨɠɧɨɝɨ ɭɞɚɥɟɧɢɹ ɩɢɬɚɬɟɥɶɧɨɣ ɫɪɟɞɵ, ɛɟɡ ɧɚɪɭɲɟɧɢɹ ɤɥɟɬɨɱɧɨɝɨ ɦɨɧɨɫɥɨɹ. Ɂɚɬɟɦ
ɤɥɟɬɤɢ ɨɬɦɵɜɚɥɢ, ɨɫɬɨɪɨɠɧɨ ɧɚɧɨɫɹ ɧɚ ɦɨɧɨɫɥɨɣ 2 ɦɥ ɯɨɥɨɞɧɨɝɨ ɛɭɮɟɪɧɨɝɨ ɪɚɫɬɜɨɪɚ ɢ ɚɤɤɭɪɚɬɧɨ ɜɫɬɪɹɯɢɜɚɹ ɤɨɥɛɭ ɫ ɤɥɟɬɨɱɧɨɣ ɤɭɥɶɬɭɪɨɣ ɩɪɢ
+4°C ɜ ɬɟɱɟɧɢɟ 5 ɦɢɧ. Ɂɚɬɟɦ ɩɪɨɦɵɜɨɱɧɵɣ ɛɭɮɟɪ ɩɨɥɧɨɫɬɶɸ ɭɞɚɥɹɟɬɫɹ, ɚ
ɨɬɦɵɜɚɧɢɟ ɩɨɜɬɨɪɹɟɬɫɹ ɞɥɹ ɭɞɚɥɟɧɢɹ ɡɚɝɪɹɡɧɹɸɳɢɯ ɤɨɦɩɨɧɟɧɬɨɜ ɩɢɬɚɬɟɥɶɧɨɣ ɫɪɟɞɵ. Ⱦɚɥɟɟ ɫɦɟɲɢɜɚɥɢ 1 ɦɥ ɨɯɥɚɠɞɟɧɧɨɝɨ ɥɶɞɨɦ Extraction
Buffer I ɢ 5 ɦɤɥ Protease Inhibitor Cocktail ɫ ɧɟɦɟɞɥɟɧɧɵɦ ɞɨɛɚɜɥɟɧɢɟɦ
ɷɬɨɣ ɫɦɟɫɢ ɜ ɤɨɥɛɭ, ɧɟ ɧɚɪɭɲɚɹ ɤɥɟɬɨɱɧɨɝɨ ɦɨɧɨɫɥɨɹ, ɞɜɢɝɚɹ ɤɨɥɛɭ ɞɨ ɬɟɯ
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ɩɨɪ, ɩɨɤɚ ɜɫɟ ɤɥɟɬɤɢ ɧɟ ɛɭɞɭɬ ɩɨɤɪɵɬɵ ɛɭɮɟɪɨɦ ɫ ɩɨɫɥɟɞɭɸɳɢɦ ɢɧɤɭɛɢɪɨɜɚɧɢɟɦ ɫɨɞɟɪɠɢɦɨɝɨ ɜ ɬɟɱɟɧɢɟ 10 ɦɢɧ ɩɪɢ ɨɫɬɨɪɨɠɧɨɦ ɜɫɬɪɹɯɢɜɚɧɢɢ.
ɋɭɩɟɪɧɚɬɚɧɬ (ɮɪɚɤɰɢɹ 1) ɡɚɬɟɦ ɩɟɪɟɧɨɫɢɥɢ ɜ ɩɪɨɛɢɪɤɭ ɫ ɩɨɦɨɳɶɸ
ɩɢɩɟɬɤɢ, ɧɟ ɧɚɪɭɲɚɹ ɤɥɟɬɨɱɧɨɝɨ ɫɥɨɹ. ȼɫɹ ɠɢɞɤɨɫɬɶ ɞɨɥɠɧɚ ɛɵɬɶ ɭɞɚɥɟɧɚ, ɚ ɮɪɚɤɰɢɹ 1 ɞɨɥɠɧɚ ɨɯɥɚɠɞɚɬɶɫɹ ɥɶɞɨɦ ɞɥɹ ɦɢɧɢɦɢɡɚɰɢɢ ɩɨɬɟɪɶ
ɨɛɪɚɡɰɚ. Ɂɚɬɟɦ ɫɦɟɲɢɜɚɥɢ 1 ɦɥ ɨɯɥɚɠɞɟɧɧɨɝɨ ɷɤɫɬɪɚɤɰɢɨɧɧɨɝɨ ɛɭɮɟɪɚ 2
ɢ 5 ɦɤɥ Protease Inhibitor Cocktail ɢ ɧɟɦɟɞɥɟɧɧɨ ɩɟɪɟɧɨɫɢɥɢ ɫɦɟɫɶ ɜ ɤɨɥɛɭ, ɧɟ ɧɚɪɭɲɚɹ ɦɨɧɨɫɥɨɣ. ȼɫɟ ɤɥɟɬɤɢ ɧɚɤɪɵɜɚɥɢ ɛɭɮɟɪɧɵɦ ɪɚɫɬɜɨɪɨɦ ɢ
ɢɧɤɭɛɢɪɨɜɚɥɢ ɜ ɬɟɱɟɧɢɟ 30 ɦɢɧ ɩɪɢ +4°C, ɫɥɟɝɤɚ ɜɫɬɪɹɯɢɜɚɹ.
ɋɭɩɟɪɧɚɬɚɧɬ (ɮɪɚɤɰɢɹ 2) ɩɟɪɟɧɨɫɢɥɢ ɜ ɩɪɨɛɢɪɤɭ ɞɥɹ ɨɛɪɚɡɰɚ ɫ
ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɩɢɩɟɬɤɢ ɛɟɡ ɧɚɪɭɲɟɧɢɹ ɰɟɥɨɫɬɧɨɫɬɢ ɤɥɟɬɨɱɧɨɝɨ ɫɥɨɹ.
Ɏɪɚɤɰɢɹ 2 ɫ ɭɞɚɥɟɧɧɨɣ ɢɡ ɧɟɟ ɠɢɞɤɨɫɬɶɸ ɯɪɚɧɢɬɫɹ ɡɚɬɟɦ ɧɚ ɥɶɞɭ.
ɋɦɟɲɢɜɚɥɢ 500 ɦɤɥ ɨɯɥɚɠɞɟɧɧɨɝɨ ɷɤɫɬɪɚɤɰɢɨɧɧɨɝɨ ɛɭɮɟɪɚ III ɫ 5 ɦɤɥ
ɤɨɤɬɟɣɥɹ ɢɧɝɢɛɢɬɨɪɚ ɩɪɨɬɟɚɡ ɢ 1,5 ɦɤɥ (• 375 U) ɛɟɧɡɨɧɚɡɵ. ɋɪɚɡɭ ɩɨɫɥɟ ɷɬɨɝɨ ɫɦɟɫɶ ɩɟɪɟɧɨɫɢɥɢ ɜ ɤɨɥɛɭ, ɧɟ ɧɚɪɭɲɚɹ ɦɨɧɨɫɥɨɹ ɢ ɨɫɬɨɪɨɠɧɨ ɞɜɢɝɚɹ ɤɨɥɛɭ, ɱɬɨɛɵ ɤɥɟɬɤɢ ɛɵɥɢ ɩɨɤɪɵɬɵ ɛɭɮɟɪɨɦ, ɡɚɬɟɦ ɢɧɤɭɛɢɪɨɜɚɥɢ ɢɯ ɩɪɢ ɨɫɬɨɪɨɠɧɨɦ ɜɫɬɪɹɯɢɜɚɧɢɢ ɜ ɬɟɱɟɧɢɟ 10 ɦɢɧ ɩɪɢ ɬɟɦɩɟɪɚɬɭɪɟ 4°C, ɞɨɫɬɢɝɚɹ ɨɩɬɢɦɚɥɶɧɨɣ ɩɪɟɰɢɩɢɬɚɰɢɢ.
ɋɭɩɟɪɧɚɬɚɧɬ (ɮɪɚɤɰɢɹ 3) ɩɟɪɟɧɨɫɢɥɢ ɜ ɩɪɨɛɢɪɤɭ ɞɥɹ ɨɛɪɚɡɰɚ ɫ
ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɩɢɩɟɬɤɢ ɛɟɡ ɧɚɪɭɲɟɧɢɹ ɰɟɥɨɫɬɧɨɫɬɢ ɤɥɟɬɨɱɧɨɝɨ ɫɥɨɹ ɢ
ɫ ɩɨɥɧɵɦ ɭɞɚɥɟɧɢɟɦ ɜɫɟɣ ɠɢɞɤɨɫɬɢ. Ʉɨɧɟɱɧɵɣ ɷɬɚɩ – ɫɦɟɲɢɜɚɧɢɟ ɩɪɢ
ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ 500 ɦɤɥ ɷɤɫɬɪɚɤɰɢɨɧɧɨɝɨ ɛɭɮɟɪɚ IV and 5 ɦɤɥ
ɤɨɤɬɟɣɥɹ ɢɧɝɢɛɢɬɨɪɚ ɩɪɨɬɟɚɡ, ɩɟɪɟɧɨɫ ɫɦɟɫɢ ɜ ɤɨɥɛɭ ɞɥɹ ɡɚɜɟɪɲɟɧɢɹ
ɫɨɥɸɛɢɥɢɡɚɰɢɢ ɨɫɬɚɬɨɱɧɨɝɨ ɦɚɬɟɪɢɚɥɚ, ɩɟɪɟɧɨɫ ɷɤɫɬɪɚɤɬɚ ɜ ɩɪɨɛɢɪɤɭ
(ɮɪɚɤɰɢɹ 4) ɢ ɯɪɚɧɟɧɢɟ ɟɟ ɧɚ ɥɶɞɭ.
ȿɫɥɢ ɷɤɫɩɟɪɢɦɟɧɬ ɩɪɨɜɨɞɢɬɫɹ ɧɟ ɫɪɚɡɭ, ɚ ɩɪɟɞɩɨɥɚɝɚɟɬɫɹ ɞɥɢɬɟɥɶɧɨɟ ɯɪɚɧɟɧɢɟ, ɚɥɢɤɜɨɬɵ (ɧɚɩɪɢɦɟɪ, 100 ɦɤɥ) ɯɪɚɧɹɬɫɹ ɩɪɢ ɬɟɦɩɟɪɚɬɭɪɟ –20°C ɢɥɢ ɛɨɥɟɟ ɧɢɡɤɨɣ.
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ɇɚ ɫɥɟɞɭɸɳɟɣ ɩɨɫɥɟ ɷɤɫɬɪɚɝɢɪɨɜɚɧɢɹ ɫɬɚɞɢɢ ɪɚɛɨɬɵ ɩɪɢɦɟɧɹɟɬɫɹ ɧɚɛɨɪ ɪɟɚɝɟɧɬɨɜ 2D Clean-Up Kit (Amersham Biosciences), ɡɚɜɟɪɲɚɸɳɢɣ ɢ ɨɩɬɢɦɢɡɢɪɭɸɳɢɣ ɩɨɞɝɨɬɨɜɤɭ ɨɛɪɚɡɰɨɜ ɤ ɞɜɭɦɟɪɧɨɦɭ ɝɟɥɶɷɥɟɤɬɪɨɮɨɪɟɡɭ. Ɋɟɚɝɟɧɬɵ ɷɬɨɝɨ ɧɚɛɨɪɚ ɤɨɥɢɱɟɫɬɜɟɧɧɨ ɨɫɚɠɞɚɸɬ ɛɟɥɤɢ, ɨɫɬɚɜɥɹɹ ɩɨɦɟɯɨɨɛɪɚɡɭɸɳɢɟ ɫɨɟɞɢɧɟɧɢɹ (ɞɟɬɟɪɝɟɧɬɵ, ɫɨɥɢ, ɥɢɩɢɞɵ, ɮɟɧɨɥɵ, ɧɭɤɥɟɢɧɨɜɵɟ ɤɢɫɥɨɬɵ) ɜ ɪɚɫɬɜɨɪɟɧɧɨɦ ɫɨɫɬɨɹɧɢɢ. Ɉɫɚɞɨɤ ɨɬɞɟɥɹɟɬɫɹ ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɧɢɟɦ, ɨɬɦɵɜɚɟɬɫɹ ɢ ɪɟɫɭɫɩɟɧɞɢɪɭɟɬɫɹ
ɜ ɞɟɧɚɬɭɪɢɪɭɸɳɟɦ ɪɚɫɬɜɨɪɟ ɞɥɹ ɨɞɧɨɦɟɪɧɨɝɨ ɢɡɨɷɥɟɤɬɪɢɱɟɫɤɨɝɨ ɮɨɤɭɫɢɪɨɜɚɧɢɹ (ɂɗɎ).
ɉɟɪɜɵɣ ɷɬɚɩ ɨɱɢɫɬɤɢ ɜɤɥɸɱɚɟɬ ɩɟɪɟɧɨɫ ɨɛɪɚɡɰɚ ɜ ɩɪɨɛɢɪɤɭ ɞɥɹ
ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɧɢɹ ɩɪɢ 8000 g. Ɂɚɬɟɦ ɭɞɚɥɹɟɬɫɹ ɫɭɩɟɪɧɚɬɚɧɬ, ɧɟ ɧɚɪɭɲɚɹ ɰɟɥɨɫɬɧɨɫɬɢ ɨɫɚɞɤɚ, ɩɨɜɬɨɪɧɨ ɩɪɨɜɨɞɢɬɫɹ ɰɟɧɬɪɢɮɭɝɢɪɨɜɚɧɢɟ
ɜ ɬɟɱɟɧɢɟ 1 ɦɢɧ ɢ ɫɧɨɜɚ ɭɞɚɥɹɸɬɫɹ ɨɫɬɚɬɤɢ ɫɭɩɟɪɧɚɬɚɧɬɚ.
Ʉɨɧɟɱɧɚɹ ɫɬɚɞɢɹ – ɪɟɫɭɫɩɟɧɞɢɪɨɜɚɧɢɟ ɤɚɠɞɨɝɨ ɨɫɚɞɤɚ (ɫɝɭɫɬɤɚ) ɜ
ɜɨɞɧɨɦ ɪɚɫɬɜɨɪɟ ɞɥɹ ɂɗɎ ɩɟɪɜɨɝɨ ɧɚɩɪɚɜɥɟɧɢɹ. Ɉɛɴɟɦ ɪɟɝɢɞɪɢɪɭɸɳɟɝɨ ɪɚɫɬɜɨɪɚ ɦɨɠɟɬ ɫɨɫɬɚɜɥɹɬɶ 1/20 ɱɚɫɬɶ ɨɬ ɨɛɴɟɦɚ ɨɪɢɝɢɧɚɥɶɧɨɝɨ
ɨɛɪɚɡɰɚ. ɉɪɨɛɢɪɤɚ ɜɫɬɪɹɯɢɜɚɟɬɫɹ ɜ ɬɟɱɟɧɢɟ 30 ɫɟɤɭɧɞ, ɢɧɤɭɛɢɪɭɟɬɫɹ
ɩɪɢ ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ ɞɨ ɩɨɥɧɨɝɨ ɪɚɫɬɜɨɪɟɧɢɹ ɫɝɭɫɬɤɚ ɢ ɰɟɧɬɪɢɮɭɝɢɪɭɟɬɫɹ ɩɪɢ 8 000g ɜ ɬɟɱɟɧɢɟ 10 ɦɢɧ ɞɥɹ ɭɞɚɥɟɧɢɹ ɧɟɪɚɫɬɜɨɪɢɦɨɝɨ ɦɚɬɟɪɢɚɥɚ. ɋɭɩɟɪɧɚɬɚɧɬ ɦɨɠɟɬ ɩɨɞɜɟɪɝɚɬɶɫɹ ɧɟɩɨɫɪɟɞɫɬɜɟɧɧɨ
ɂɗɎ ɢɥɢ ɩɟɪɟɧɨɫɢɬɶɫɹ ɜ ɞɪɭɝɭɸ ɩɪɨɛɢɪɤɭ ɞɥɹ ɯɪɚɧɟɧɢɹ ɩɪɢ –80ºC
ɞɥɹ ɩɨɫɥɟɞɭɸɳɢɯ ɚɧɚɥɢɡɨɜ.
2.7. ɉɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɶ (ɚɥɝɨɪɢɬɦ) ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ
Ⱥɥɝɨɪɢɬɦ ɷɮɮɟɤɬɢɜɧɨɝɨ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ ɬɪɟɛɭɟɬ ɧɟ ɬɨɥɶɤɨ
ɫɬɚɧɞɚɪɬɢɡɚɰɢɢ, ɧɨ ɢ ɚɜɬɨɦɚɬɢɡɚɰɢɢ ɛɨɥɶɲɢɧɫɬɜɚ ɫɜɨɢɯ ɫɬɚɞɢɣ. ɀɟɥɚɬɟɥɶɧɨ ɬɚɤɠɟ ɪɚɡɪɟɲɟɧɢɟ, ɩɨɡɜɨɥɹɸɳɟɟ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɬɶ ɦɚɤɫɢɦɚɥɶɧɨ ɜɨɡɦɨɠɧɨɟ ɤɨɥɢɱɟɫɬɜɨ ɛɟɥɤɨɜ. Ɋɚɡɧɵɟ ɷɬɚɩɵ ɚɥɝɨɪɢɬɦɚ ɞɨɥɠ-
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ɧɵ ɛɵɬɶ ɫɨɜɦɟɫɬɢɦɵ ɞɪɭɝ ɫ ɞɪɭɝɨɦ ɞɥɹ ɢɫɤɥɸɱɟɧɢɹ ɨɲɢɛɨɤ ɨɩɟɪɚɬɨɪɨɜ ɢ ɩɪɢɞɚɧɢɹ ɩɪɨɰɟɫɫɭ ɯɚɪɚɤɬɟɪɢɫɬɢɤ ɜɨɫɩɪɨɢɡɜɨɞɢɦɨɫɬɢ ɩɪɢ ɜɵɫɨɤɨɣ ɩɪɨɢɡɜɨɞɢɬɟɥɶɧɨɫɬɢ. Ɍɪɟɛɭɟɬɫɹ ɬɚɤɠɟ ɨɩɪɟɞɟɥɢɬɶ ɫɬɚɪɬɨɜɵɟ
ɛɚɡɨɜɵɟ ɩɚɪɚɦɟɬɪɵ ɛɟɥɤɨɜ ɞɨ ɧɚɱɚɥɚ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ ɤɥɟɬɨɤ, ɱɬɨ ɩɨɡɜɨɥɢɬ ɜ ɞɚɥɶɧɟɣɲɟɦ ɪɟɝɢɫɬɪɢɪɨɜɚɬɶ ɢɯ ɞɢɧɚɦɢɤɭ (ɞɟɝɪɚɞɚɰɢɸ ɢɥɢ
ɦɨɞɢɮɢɤɚɰɢɸ). ɇɚɦɢ ɩɪɟɞɥɨɠɟɧɚ ɩɪɨɰɟɞɭɪɚ ɨɩɪɟɞɟɥɟɧɢɹ ɬ.ɧ. ɪɟɮɟɪɟɧɫɧɨɣ (ɷɬɚɥɨɧɧɨɣ) ɬɨɱɤɢ ɞɥɹ ɢɫɫɥɟɞɨɜɚɧɢɹ ȽɋɄ ɜ ɜɢɞɟ ɩɨɥɭɚɜɬɨɦɚɬɢɡɢɪɨɜɚɧɧɨɝɨ ɚɥɝɨɪɢɬɦɚ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ.
Ʉɥɸɱɟɜɨɣ ɦɨɦɟɧɬ ɩɨɥɭɱɟɧɢɹ CD34+ ɤɥɟɬɨɤ ɢɡ ɨɛɪɚɡɰɚ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ – ɜɵɞɟɥɟɧɢɟ ɞɨɫɬɚɬɨɱɧɨɝɨ ɤɨɥɢɱɟɫɬɜɚ ɤɥɟɬɨɤ, ɧɟɨɛɯɨɞɢɦɵɯ
ɞɥɹ ɚɧɚɥɢɡɚ, ɚ ɷɬɨ – ɦɢɧɢɦɭɦ ɞɜɚ ɦɢɥɥɢɨɧɚ ɤɥɟɬɨɤ. ȿɫɥɢ ɨɛɪɚɡɟɰ ɫɨɞɟɪɠɢɬ ɛɨɥɶɲɟɟ ɤɨɥɢɱɟɫɬɜɨ ɤɥɟɬɨɤ, ɟɝɨ ɪɚɡɛɚɜɥɹɸɬ ɞɨ ɦɢɧɢɦɚɥɶɧɨɝɨ
ɡɧɚɱɟɧɢɹ ɫɨɞɟɪɠɚɧɢɹ ɤɥɟɬɨɤ. Ɇɵ ɩɨɞɱɟɪɤɢɜɚɟɦ ɜɚɠɧɨɫɬɶ ɫɨɯɪɚɧɟɧɢɹ
ɫɬɚɧɞɚɪɬɢɡɢɪɨɜɚɧɧɨɝɨ ɤɨɥɢɱɟɫɬɜɚ ɨɛɪɚɡɰɚ, ɡɚɝɪɭɠɚɟɦɨɝɨ ɧɚ ɩɥɚɫɬɢɧɵ
ɞɥɹ ɂɗɎ ɜ ɩɟɪɜɨɦ ɧɚɩɪɚɜɥɟɧɢɢ 2D. Ʉɨɥɢɱɟɫɬɜɨ ɢɦɟɧɧɨ ɜ ɞɜɚ ɦɢɥɥɢɨɧɚ ɤɥɟɬɨɤ ɛɵɥɨ ɨɩɪɟɞɟɥɟɧɨ ɦɟɬɨɞɨɦ ɩɪɨɛ ɢ ɨɲɢɛɨɤ ɢ ɩɪɢɡɧɚɧɨ
ɭɞɨɜɥɟɬɜɨɪɢɬɟɥɶɧɵɦ ɞɥɹ ȽɋɄ ɩɨ ɤɪɢɬɟɪɢɸ ɪɚɡɞɟɥɟɧɢɹ ɛɟɥɤɨɜ ɧɚ ɝɟɥɟ
ɢ ɞɨɫɬɨɜɟɪɧɨɣ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ.
Ɉɞɧɢɦ ɢɡ ɷɥɟɦɟɧɬɨɜ ɧɨɜɢɡɧɵ ɜ ɢɡɭɱɟɧɢɢ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɹɜɥɹɟɬɫɹ ɩɪɟɞɥɚɝɚɟɦɨɟ ɧɚɦɢ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɟ ɨɛɪɚɡɰɚ ɞɨ ɩɪɨɬɟɨɦɧɨɝɨ
ɚɧɚɥɢɡɚ. ɇɚɛɨɪ ɞɥɹ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɹ ɩɨɡɜɨɥɹɟɬ ɞɨɫɬɢɝɧɭɬɶ ɫɪɚɡɭ
ɧɟɫɤɨɥɶɤɨ ɰɟɥɟɣ: ɥɢɡɢɪɨɜɚɬɶ ɤɥɟɬɤɢ, ɩɪɨɜɟɫɬɢ ɨɱɢɫɬɤɭ ɢ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɟ ɨɛɪɚɡɰɚ. Ɉɛɪɚɡɟɰ ɞɟɥɢɬɫɹ ɧɚ ɬɪɢ ɮɪɚɤɰɢɢ (ɢɥɢ ɱɟɬɵɪɟ) ɫ ɜɨɡɪɚɫɬɚɸɳɟɣ ɝɢɞɪɨɮɨɛɧɨɫɬɶɸ (ɫɧɢɠɚɸɳɟɣɫɹ ɪɚɫɬɜɨɪɢɦɨɫɬɶɸ). ɗɬɨ
ɨɛɟɫɩɟɱɢɜɚɟɬ ɧɚɫ ɬɪɟɦɹ-ɱɟɬɵɪɶɦɹ ɩɨɪɰɢɹɦɢ ɤɥɟɬɨɱɧɨɝɨ ɫɨɞɟɪɠɢɦɨɝɨ
ɢ ɩɨɡɜɨɥɹɟɬ ɪɚɡɞɟɥɢɬɶ ɛɟɥɤɢ ɫ ɭɥɭɱɲɟɧɧɨɣ ɫɬɟɩɟɧɶɸ ɧɚɞɟɠɧɨɫɬɢ.
ȼɦɟɫɬɨ ɝɟɥɹ ɫ ɫɨɬɧɹɦɢ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɪɟɡɭɥɶɬɚɬɨɦ ɹɜɥɹɟɬɫɹ ɪɚɫɩɪɟɞɟɥɟɧɢɟ ɫɨɬɟɧ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɧɚ ɬɪɟɯ-ɱɟɬɵɪɟɯ ɝɟɥɹɯ. Ɋɚɡɪɟɲɟɧɢɟ
46
ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɨɛɵɱɧɨ ɞɨɫɬɢɝɚɟɬɫɹ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɝɟɥɟɣ ɛɨɥɶɲɟɣ
ɜɟɥɢɱɢɧɵ, ɨɞɧɚɤɨ ɫ ɧɢɦɢ ɬɪɭɞɧɟɟ ɪɚɛɨɬɚɬɶ ɢ ɨɧɢ ɛɨɥɟɟ ɩɨɞɜɟɪɠɟɧɵ
ɪɚɡɪɵɜɭ. ɂɫɩɨɥɶɡɨɜɚɧɢɟ ɝɟɥɟɣ ɦɟɧɶɲɟɝɨ ɮɨɪɦɚɬɚ (4–12% ɝɪɚɞɢɟɧɬɧɵɣ ɉȺȺȽ Criterion XT, Bio-Rad) ɨɤɚɡɚɥɨɫɶ ɨɩɬɢɦɚɥɶɧɵɦ ɞɥɹ ɭɥɭɱɲɟɧɧɨɝɨ ɪɚɡɞɟɥɟɧɢɹ ɛɟɥɤɨɜ.
2.8. Ɋɚɡɞɟɥɟɧɢɟ ɛɟɥɤɨɜ ɫ ɩɨɦɨɳɶɸ ɞɜɭɦɟɪɧɨɝɨ ɝɟɥɶ-ɷɥɟɤɬɪɨɮɨɪɟɡɚ
ɉɪɨɜɨɞɢɥɢ ɚɧɚɥɢɬɢɱɟɫɤɨɟ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɟ ɩɨ ɞɜɭɦ ɧɟɡɚɜɢɫɢɦɵɦ ɞɪɭɝ ɨɬ ɞɪɭɝɚ ɮɢɡɢɤɨ-ɯɢɦɢɱɟɫɤɢɦ ɫɜɨɣɫɬɜɚɦ ɩɨɥɢɩɟɩɬɢɞɧɵɯ ɰɟɩɟɣ, ɨɬɪɚɠɚɸɳɢɯ ɨɫɨɛɟɧɧɨɫɬɢ ɢɯ ɩɟɪɜɢɱɧɨɣ ɫɬɪɭɤɬɭɪɵ: ɂɗɎ ɨɛɟɫɩɟɱɢɜɚɟɬ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɟ ɩɨ pI; ɷɥɟɤɬɪɨɮɨɪɟɡ ɜ ɩɪɢɫɭɬɫɬɜɢɢ SDS
ɨɛɟɫɩɟɱɢɜɚɟɬ ɪɚɡɞɟɥɟɧɢɟ ɩɨ ɦɨɥɟɤɭɥɹɪɧɵɦ ɜɟɫɚɦ. Ⱦɥɹ ɥɭɱɲɟɣ ɪɚɡɪɟɲɚɸɳɟɣ ɫɩɨɫɨɛɧɨɫɬɢ ɢɫɩɨɥɶɡɨɜɚɥɢɫɶ ɝɪɚɞɢɟɧɬɧɵɟ ɝɟɥɢ, ɬ.ɟ. ɪɚɡɦɟɪ
ɩɨɪ ɦɚɬɪɢɤɫɚ ɫɧɢɠɚɥɫɹ ɩɨ ɧɚɩɪɚɜɥɟɧɢɸ ɤ ɧɢɡɭ ɝɟɥɹ ɞɥɹ ɡɚɞɟɪɠɚɧɢɹ
ɛɟɥɤɨɜ ɦɟɧɶɲɟɝɨ ɪɚɡɦɟɪɚ.
ɉɟɪɜɨɟ ɧɚɩɪɚɜɥɟɧɢɟ 2D ɩɪɢɦɟɧɹɟɬɫɹ ɞɥɹ ɪɚɡɞɟɥɟɧɢɹ ɛɟɥɤɨɜ ɜ ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɢɯ ɡɚɪɹɞɨɦ. ɋ ɷɬɨɣ ɰɟɥɶɸ ɢɫɩɨɥɶɡɭɸɬɫɹ ɬ.ɧ. ɢɡɨɷɥɟɤɬɪɢɱɟɫɤɢɟ ɫɬɪɢɩɵ ɫ ɪɇ 3–11. ɉɪɨɬɨɤɨɥ ɢɡɨɷɥɟɤɬɪɢɱɟɫɤɨɝɨ ɮɨɤɭɫɢɪɨɜɚɧɢɹ ɛɟɥɤɨɜ ɛɵɥ ɨɩɬɢɦɢɡɢɪɨɜɚɧ ɞɨ ɩɹɬɢ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɵɯ ɫɬɚɞɢɣ:
1) ɡɚɝɪɭɡɤɚ ɧɚ 3 ɱɚɫ ɩɪɢ 200 ȼ, 2) ɩɨɫɬɟɩɟɧɧɨɟ ɭɜɟɥɢɱɟɧɢɟ ɧɚɩɪɹɠɟɧɢɹ
ɞɨ 1000 ȼ ɜ ɬɟɱɟɧɢɟ 6 ɱɚɫ, 3) ɭɜɟɥɢɱɟɧɢɟ ɧɚɩɪɹɠɟɧɢɹ ɞɨ 8000 ȼ ɧɚ
3 ɱɚɫɚ (ɮɨɤɭɫɢɪɨɜɚɧɢɟ), ɜɵɞɟɪɠɢɜɚɧɢɟ ɩɪɢ 5090 ȼ ɜ ɬɟɱɟɧɢɟ 6 ɱɚɫ, 5)
ɜɵɞɟɪɠɢɜɚɧɢɟ ɜ ɬɟɱɟɧɢɟ 5 ɦɢɧ ɩɪɢ 8000 ȼ (ɮɢɧɚɥɶɧɨɟ ɮɨɤɭɫɢɪɨɜɚɧɢɟ). 12–15 Ʉɜ/ɱɚɫ – ɨɩɬɢɦɚɥɶɧɨ ɞɥɹ ɞɨɫɬɢɠɟɧɢɹ ɯɨɪɨɲɟɝɨ ɪɚɡɞɟɥɟɧɢɹ ɜ ɩɟɪɜɨɦ ɧɚɩɪɚɜɥɟɧɢɢ ɞɥɹ ȽɋɄ. Ɇɚɤɫɢɦɚɥɶɧɨɟ ɧɚɩɪɹɠɟɧɢɟ ɞɥɹ
ɫɬɚɞɢɣ 3 ɢ 5–8000 ȼ, ɞɥɹ ɨɛɪɚɡɰɨɜ ɫ ɜɵɫɨɤɨɣ ɩɪɨɜɨɞɢɦɨɫɬɶɸ ɢ ɧɢɡɤɢɦ ɫɨɩɪɨɬɢɜɥɟɧɢɟɦ ɞɨɫɬɚɬɨɱɧɨ 4000 ȼ.
47
ȼɬɨɪɨɟ ɧɚɩɪɚɜɥɟɧɢɟ 2D ɩɨɡɜɨɥɹɟɬ ɪɚɡɞɟɥɢɬɶ ɛɟɥɤɢ, ɢɦɟɸɳɢɟ
ɪɚɡɧɵɣ ɦɨɥɟɤɭɥɹɪɧɵɣ ɜɟɫ. ɉȺȺȽ (Criterion XT, Bio-Rad) ɫ ɝɪɚɞɢɟɧɬɨɦ 4–12% ɩɨɡɜɨɥɹɟɬ ɪɚɡɞɟɥɢɬɶ ɛɟɥɤɢ ɫ ɦɨɥɟɤɭɥɹɪɧɵɦ ɜɟɫɨɦ ɨɬ 10
ɞɨ 200 kDa.
2.9. Ɉɤɪɚɲɢɜɚɧɢɟ (ɞɟɬɟɤɰɢɹ) ɢ ɜɢɡɭɚɥɢɡɚɰɢɹ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ
Ⱦɥɹ ɨɤɪɚɲɢɜɚɧɢɹ ɛɟɥɤɨɜ ɢɫɩɨɥɶɡɨɜɚɥɫɹ ɤɭɦɚɫɫɢ-ɩɨɞɨɛɧɵɣ ɤɪɚɫɢɬɟɥɶ (Imperial™, ThermoFisher Scientific). Ɉɧ ɞɚɜɚɥ ɥɭɱɲɢɟ ɪɟɡɭɥɶɬɚɬɵ
(ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɶ 6 ɧɝ ɛɟɥɤɚ, ɢɡɛɢɪɚɬɟɥɶɧɨɫɬɶ), ɱɟɦ ɩɪɨɱɢɟ ɧɟɮɥɭɨɪɟɫɰɟɧɬɧɵɟ ɤɨɦɦɟɪɱɟɫɤɢ ɞɨɫɬɭɩɧɵɟ ɤɪɚɫɢɬɟɥɢ. Ʉɪɚɫɢɬɟɥɶ ɜɡɚɢɦɨɞɟɣɫɬɜɨɜɚɥ
ɫ ɝɟɥɟɦ ɜ ɬɟɱɟɧɢɟ ɨɞɧɨɝɨ ɱɚɫɚ. Ⱦɥɹ ɩɨɜɵɲɟɧɢɹ ɤɨɧɬɪɚɫɬɧɨɫɬɢ ɝɟɥɶ ɡɚɬɟɦ
ɨɛɪɚɛɚɬɵɜɚɥɢ ɜɨɞɨɣ MilliQ ɜ ɬɟɱɟɧɢɟ ɧɨɱɢ. Ȼɟɥɤɨɜɵɟ ɩɹɬɧɚ ɩɪɢɨɛɪɟɬɚɥɢ
ɫɜɟɬɥɨ-ɩɭɪɩɭɪɧɵɣ ɰɜɟɬ ɢ ɱɟɬɤɨɫɬɶ, ɫɩɨɫɨɛɫɬɜɭɸɳɭɸ ɩɨɫɥɟɞɭɸɳɟɦɭ ɜɵɪɟɡɚɧɢɸ. ȼɢɡɭɚɥɢɡɚɰɢɹ ɨɤɪɚɲɟɧɧɵɯ ɝɟɥɟɣ ɩɪɨɜɨɞɢɥɚɫɶ ɫ ɩɨɦɨɳɶɸ ɩɪɢɛɨɪɚ Dyversity (Syngene). ɗɬɚ ɩɪɨɰɟɞɭɪɚ ɡɚɧɢɦɚɥɚ 1–2 ɦɢɧ. ɋɤɚɧɢɪɨɜɚɧɧɵɟ ɫɧɢɦɤɢ (ɢɡɨɛɪɚɠɟɧɢɹ) ɩɨɞɜɟɪɝɚɥɢɫɶ ɚɧɚɥɢɡɭ ɞɥɹ ɨɛɧɚɪɭɠɟɧɢɹ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ, ɱɬɨ ɩɨɡɜɨɥɹɥɨ ɩɪɨɜɨɞɢɬɶ ɢɯ ɜɵɪɟɡɚɧɢɟ ɢ ɢɞɟɧɬɢɮɢɤɚɰɢɸ
ɛɟɥɤɨɜ. ɉɨɫɥɟ ɪɚɡɞɟɥɟɧɢɹ ɞɜɭɦɟɪɧɵɦ ɷɥɟɤɬɪɨɮɨɪɟɡɨɦ ɢ ɨɤɪɚɲɢɜɚɧɢɹ
Ʉɭɦɚɫɫɢ R350 ɤɭɫɨɱɤɢ ɝɟɥɹ ɞɢɚɦɟɬɪɨɦ 1–1,5 ɦɦ, ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɟ ɛɟɥɤɨɜɵɦ ɩɹɬɧɚɦ, ɜɵɪɟɡɚɥɢ.
2.10. Ⱥɧɚɥɢɡ ɢɡɨɛɪɚɠɟɧɢɣ ɢ ɢɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ
Ⱦɥɹ ɞɟɬɟɤɬɢɪɨɜɚɧɢɹ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɢ ɤɨɦɩɶɸɬɟɪɧɨɝɨ ɚɧɚɥɢɡɚ
ɢɡɨɛɪɚɠɟɧɢɣ ɢɫɩɨɥɶɡɨɜɚɥɚɫɶ ɩɪɨɝɪɚɦɦɚ 2D Evolution/SameSpots (Nonlinear Dynamics). Ʉɨɦɩɶɸɬɟɪɧɵɣ ɚɧɚɥɢɡ ɩɪɢɦɟɧɹɥɫɹ ɬɚɤɠɟ ɞɥɹ ɫɪɚɜɧɟɧɢɹ ɪɚɡɧɵɯ ɝɟɥɟɣ, ɩɪɟɞɫɬɚɜɥɹɸɳɢɯ ɪɚɡɧɵɟ ɨɛɪɚɡɰɵ ɤɥɟɬɨɱɧɨɝɨ ɫɨɞɟɪɠɢɦɨɝɨ ɜ ɫɨɱɟɬɚɧɢɢ ɫɨ ɫɤɚɧɟɪɨɦ ɜɵɫɨɤɨɝɨ ɪɚɡɪɟɲɟɧɢɹ (UMAX
scanner) ɢ/ɢɥɢ ɩɪɢɛɨɪɚ ɞɥɹ ɜɢɡɭɚɥɢɡɚɰɢɢ Dyversity (Syngene).
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Ⱦɥɹ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɩɹɬɟɧ ɢɯ ɜɵɪɟɡɚɥɢ (ɜɪɭɱɧɭɸ ɢɥɢ ɚɜɬɨɦɚɬɢɱɟɫɤɢ ɫ ɩɨɦɨɳɶɸ Gelpix, Genetix) ɫ ɩɨɫɥɟɞɭɸɳɟɣ ɬɪɢɩɫɢɧɢɡɚɰɢɟɣ.
ɉɨɥɭɱɟɧɧɵɟ ɩɟɩɬɢɞɵ ɚɧɚɥɢɡɢɪɨɜɚɥɢɫɶ ɧɚ MALDI ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɟ
(MicroMass). ɂɞɟɧɬɢɮɢɤɚɰɢɸ ɛɟɥɤɨɜ ɩɨ «ɩɟɩɬɢɞɧɨɦɭ ɮɢɧɝɟɪɩɪɢɧɬɭ»
ɨɫɭɳɟɫɬɜɥɹɥɢ ɩɪɢ ɩɨɦɨɳɢ ɩɪɨɝɪɚɦɦɵ Mascot ɜ ɛɚɡɟ ɞɚɧɧɵɯ NCBI ɫ
ɭɱɟɬɨɦ ɜɨɡɦɨɠɧɨɝɨ ɨɤɢɫɥɟɧɢɹ ɦɟɬɢɨɧɢɧɨɜ ɤɢɫɥɨɪɨɞɨɦ ɜɨɡɞɭɯɚ ɢ ɦɨɞɢɮɢɤɚɰɢɢ ɰɢɫɬɟɢɧɨɜ ɚɤɪɢɥɚɦɢɞɨɦ.
2.11. Ⱥɧɚɥɢɡ ɞɜɭɦɟɪɧɵɯ ɝɟɥɟɣ
Ⱥɧɚɥɢɡ ɝɟɥɟɜɵɯ ɢɡɨɛɪɚɠɟɧɢɣ ɛɟɥɤɚ (ɪɢɫ. 2.2) ɩɪɨɢɡɜɨɞɢɥɫɹ ɩɪɢ ɢɫɩɨɥɶɡɨɜɚɧɢɢ ɩɪɨɝɪɚɦɦɧɨɝɨ ɨɛɟɫɩɟɱɟɧɢɹ SameSpots (Nonlinear Dynamics).
ɗɬɚ ɩɪɨɝɪɚɦɦɚ ɩɨɡɜɨɥɹɟɬ ɨɛɧɚɪɭɠɢɬɶ ɤɚɠɞɨɟ ɢɧɞɢɜɢɞɭɚɥɶɧɨɟ ɩɹɬɧɨ,
ɩɪɢɫɜɨɢɬɶ ɟɦɭ ɧɨɦɟɪ ɢ ɤɨɥɢɱɟɫɬɜɟɧɧɨ ɨɰɟɧɢɬɶ ɜ ɬɟɪɦɢɧɚɯ ɰɜɟɬɨɜɨɣ ɢɧɬɟɧɫɢɜɧɨɫɬɢ. Ⱦɥɹ ɰɟɥɟɣ ɤɚɪɬɢɪɨɜɚɧɢɹ ɩɪɨɬɟɨɦɚ ȽɋɄ ɤɨɥɢɱɟɫɬɜɟɧɧɚɹ
ɨɰɟɧɤɚ ɢɧɬɟɧɫɢɜɧɨɫɬɢ ɨɤɪɚɲɢɜɚɧɢɹ (ɞɪɭɝɢɦɢ ɫɥɨɜɚɦɢ – ɨɰɟɧɤɚ ɤɨɥɢɱɟɫɬɜɚ ɛɟɥɤɚ) ɧɟ ɹɜɥɹɟɬɫɹ ɨɛɹɡɚɬɟɥɶɧɨɣ. Ʉɨɥɢɱɟɫɬɜɟɧɧɵɣ ɚɧɚɥɢɡ ɛɟɥɤɨɜ ɩɨɥɟɡɟɧ ɞɥɹ ɪɚɡɞɟɥɟɧɢɹ ɩɹɬɟɧ ɢ ɞɥɹ ɨɩɪɟɞɟɥɟɧɢɹ ɩɪɟɞɟɥɨɜ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ ɞɥɹ ɪɚɡɧɵɯ ɛɟɥɤɨɜɵɯ ɤɪɚɫɢɬɟɥɟɣ.
2.12. ȼɵɪɟɡɚɧɢɟ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ
ɗɬɚ ɩɪɨɰɟɞɭɪɚ ɛɵɥɚ ɚɜɬɨɦɚɬɢɡɢɪɨɜɚɧɚ ɢ ɨɫɭɳɟɫɬɜɥɹɥɚɫɶ ɫ ɩɨɦɨɳɶɸ ɪɨɛɨɬɚ Gelpix (Genetix). ɋɩɢɫɨɤ ɩɹɬɟɧ ɞɥɹ ɜɵɪɟɡɚɧɢɹ ɫɨɡɞɚɟɬɫɹ ɧɚ
ɫɬɚɞɢɢ ɚɧɚɥɢɡɚ ɢɡɨɛɪɚɠɟɧɢɣ ɛɟɥɤɨɜɵɯ ɝɟɥɟɣ. Ʉɚɠɞɨɟ ɜɵɪɟɡɚɧɧɨɟ ɩɹɬɧɨ ɢɦɟɟɬ ɞɢɚɦɟɬɪ 2 ɦɦ ɢ ɜɵɫɨɬɭ, ɫɨɨɬɜɟɬɫɬɜɭɸɳɭɸ ɝɥɭɛɢɧɟ ɝɟɥɹ.
ɉɨɫɥɟ ɜɵɪɟɡɚɧɢɹ ɩɹɬɧɨ ɩɟɪɟɧɨɫɢɬɫɹ ɧɚ 96-ɹɱɟɟɱɧɭɸ ɩɥɚɫɬɢɧɭ
(ɩɥɚɲɤɭ) ɢ ɩɨɤɪɵɜɚɟɬɫɹ ɧɟɛɨɥɶɲɢɦ ɤɨɥɢɱɟɫɬɜɨɦ ɜɨɞɵ ɞɥɹ ɩɪɟɞɨɬɜɪɚɳɟɧɢɹ ɜɵɫɵɯɚɧɢɹ ɩɟɪɟɞ ɬɪɢɩɫɢɧɢɡɚɰɢɟɣ. Ɋɨɛɨɬ ɜɵɞɚɟɬ ɪɚɫɩɟɱɚɬɤɭ, ɫɜɹɡɵɜɚɸɳɭɸ ɧɨɦɟɪ ɩɹɬɧɚ ɫ ɧɨɦɟɪɨɦ ɹɱɟɣɤɢ.
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Ⱦɥɹ ɩɨɜɵɲɟɧɢɹ ɷɮɮɟɤɬɢɜɧɨɫɬɢ ɪɚɛɨɬɵ ɪɨɛɨɬɚ ɫɨɫɬɚɜɥɹɟɬɫɹ ɫɩɟɰɢɚɥɶɧɚɹ ɤɨɨɪɞɢɧɚɬɧɚɹ ɤɚɪɬɚ, ɨɛɪɚɡɭɸɳɚɹ ɜ ɜɢɞɟ ɬɪɟɭɝɨɥɶɧɢɤɚ ɨɛɪɚɡ,
ɚɧɚɥɢɡɢɪɭɟɦɵɣ ɫ ɩɨɦɨɳɶɸ ɤɨɦɩɶɸɬɟɪɧɨɣ ɩɪɨɝɪɚɦɦɵ (ɪɢɫ. 2.2) ɫ ɨɛɪɚɡɨɦ, ɩɪɨɢɡɜɨɞɢɦɵɦ ɜɵɪɟɡɚɸɳɢɦ ɪɨɛɨɬɨɦ. ɗɬɨ ɞɟɥɚɟɬɫɹ ɞɥɹ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɪɨɛɨɬɨɦ ɜɵɛɪɚɧɧɵɯ ɤɨɨɪɞɢɧɚɬ, ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɯ ɤɚɠɞɨɦɭ ɢɧɞɢɜɢɞɭɚɥɶɧɨɦɭ ɩɹɬɧɭ.
Ɋɢɫ. 2.2. Ɍɪɟɭɝɨɥɶɧɵɟ ɤɨɨɪɞɢɧɚɬɵ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ – ɩɹɬɧɚ ɜɵɪɟɡɚɸɬɫɹ
ɜɧɭɬɪɢ ɩɥɨɳɚɞɢ ɬɪɟɭɝɨɥɶɧɢɤɚ. Ɂɧɚɤɨɦ ɏ ɩɨɦɟɱɟɧɵ ɜɵɪɟɡɚɧɧɵɟ ɩɹɬɧɚ
50
2.13. ɉɟɪɟɜɚɪɢɜɚɧɢɟ ɛɟɥɤɚ ɬɪɢɩɫɢɧɨɦ
Ȼɟɡ ɩɟɪɟɜɚɪɢɜɚɧɢɹ ɬɪɢɩɫɢɧɨɦ ɧɟɜɨɡɦɨɠɧɨ ɩɪɢɫɜɨɟɧɢɟ ɛɟɥɤɭ
ɢɞɟɧɬɢɮɢɤɚɰɢɨɧɧɨɝɨ ɧɨɦɟɪɚ (id). ȼ ɷɬɨɣ ɫɜɹɡɢ ɢɫɩɨɥɶɡɭɟɬɫɹ ɜɵɫɨɤɨɤɚɱɟɫɬɜɟɧɧɵɣ ɮɟɪɦɟɧɬ – ɬɪɢɩɫɢɧ (Promega), ɤɨɬɨɪɵɣ ɪɚɫɬɜɨɪɹɸɬ ɜ
ɛɭɮɟɪɟ ɜ ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɪɟɤɨɦɟɧɞɚɰɢɟɣ ɩɪɨɢɡɜɨɞɢɬɟɥɹ. ɉɨɷɬɚɩɧɚɹ
ɩɪɨɰɟɞɭɪɚ ɩɟɪɟɜɚɪɢɜɚɧɢɹ ɬɪɢɩɫɢɧɨɦ ɩɨɡɜɨɥɹɟɬ ɷɤɫɬɪɚɝɢɪɨɜɚɬɶ ɦɚɤɫɢɦɚɥɶɧɨɟ ɤɨɥɢɱɟɫɬɜɨ ɛɟɥɤɚ ɢɡ ɜɵɪɟɡɚɧɧɨɝɨ ɫɬɨɥɛɢɤɚ ɝɟɥɹ.
ɉɪɨɰɟɫɫ ɩɟɪɟɜɚɪɢɜɚɧɢɹ ɛɟɥɤɚ ɛɵɥ ɚɜɬɨɦɚɬɢɡɢɪɨɜɚɧ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɪɨɛɨɬɚ (GE healthcare). ɉɚɧɟɥɶ ɭɩɪɚɜɥɟɧɢɹ ɪɨɛɨɬɨɦ ɩɨɤɚɡɚɧɚ
ɧɚ ɪɢɫ. 2.3.
Ɋɢɫ. 2.3. ɉɚɧɟɥɶ ɭɩɪɚɜɥɟɧɢɹ ɪɨɛɨɬɨɦ ɩɟɪɟɜɚɪɢɜɚɧɢɹ ɛɟɥɤɚ
51
Ⱥɜɬɨɦɚɬɢɡɢɪɨɜɚɧɧɨɟ ɩɟɪɟɜɚɪɢɜɚɧɢɟ ɛɟɥɤɨɜ ɜɤɥɸɱɚɟɬ ɫɥɟɞɭɸɳɢɟ
ɫɬɚɞɢɢ:
1) ɍɞɚɥɟɧɢɟ ɨɫɬɚɬɨɱɧɨɣ ɜɨɞɵ ɢɡ ɢɫɯɨɞɧɨɝɨ ɨɛɪɚɡɰɚ.
2) ɂɧɤɭɛɚɰɢɸ ɝɟɥɟɜɨɝɨ ɫɬɨɥɛɢɤɚ ɜ ɬɟɱɟɧɢɟ 20 ɦɢɧ ɚɦɢɧɨɛɢɤɚɪɛɨɧɚɬɨɦ-ɦɟɬɚɧɨɥɨɦ.
3) ɉɪɨɦɵɜɤɚ ɝɟɥɟɜɨɝɨ ɫɬɨɥɛɢɤɚ ɚɦɢɧɨɛɢɤɚɪɛɨɧɚɬɨɦ.
4) Ɉɛɟɡɜɨɠɢɜɚɧɢɟ ɫɬɨɥɛɢɤɚ ɜ ɬɟɱɟɧɢɟ 120 ɦɢɧ 60% ɪɚɫɬɜɨɪɨɦ
ɚɰɟɬɨɧɢɬɪɢɥɚ.
5) ɍɞɚɥɟɧɢɟ ɨɫɬɚɬɤɨɜ ɠɢɞɤɨɫɬɢ ɢ ɜɵɫɭɲɢɜɚɧɢɟ ɜ ɬɟɱɟɧɢɟ 10 ɦɢɧ.
6) ɉɟɪɟɜɚɪɢɜɚɧɢɟ – ɞɨɛɚɜɥɟɧɢɟ 20 ɦɤɥ ɮɟɪɦɟɧɬɚ ɢ ɢɧɤɭɛɚɰɢɹ ɜ
ɬɟɱɟɧɢɟ 360 ɦɢɧ.
2.14. Ɉɫɨɛɟɧɧɨɫɬɢ ɚɧɚɥɢɡɚ ɤɚɪɞɢɨɩɪɟɩɚɪɚɬɨɜ
Ⱦɥɹ ɩɪɨɜɟɞɟɧɢɹ 2D ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɩɪɟɩɚɪɚɬɨɜ ɢɡ ɚɨɪɬɵ 250 ɦɤɝ
ɷɤɫɬɪɚɝɢɪɨɜɚɧɧɨɝɨ ɛɟɥɤɚ ɨɛɟɫɫɨɥɢɜɚɥɢ ɩɭɬɟɦ ɮɢɥɶɬɪɨɜɚɧɢɹ ɧɚ ɤɨɥɨɧɤɚɯ Spin-X (Costar). Ⱦɚɥɟɟ ɢɫɫɥɟɞɭɟɦɵɣ ɨɛɪɚɡɟɰ ɨɱɢɳɚɥɢ ɢ ɨɫɚɠɞɚɥɢ
ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɧɚɛɨɪɚ 2D-Clean-up (GE Healthcare) ɜ ɫɨɨɬɜɟɬɫɬɜɢɢ
ɫ ɢɧɫɬɪɭɤɰɢɟɣ ɩɪɨɢɡɜɨɞɢɬɟɥɹ. ɉɨɫɥɟ ɨɛɟɫɫɨɥɢɜɚɧɢɹ ɨɛɪɚɡɰɵ ɪɟɫɭɫɩɟɧɞɢɪɨɜɚɥɢ ɜ ɪɟɝɢɞɪɚɬɢɪɭɸɳɟɦ ɛɭɮɟɪɟ. Ⱦɥɹ ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɜ ɩɟɪɜɨɦ
ɢɡɦɟɪɟɧɢɢ ɤ ɨɛɪɚɡɰɚɦ ɞɨɛɚɜɥɹɥɢ ɬɪɢɛɭɬɢɥɮɨɫɮɢɧ ɜ ɤɚɱɟɫɬɜɟ ɜɨɫɫɬɚɧɨɜɢɬɟɥɹ ɢ ɚɦɮɨɥɢɬɵ (Bio-Rad), ɷɥɟɤɬɪɨɮɨɪɟɡ ɩɪɨɜɨɞɢɥɢ ɜ ɩɨɥɢɚɤɪɢɥɚɦɢɞɧɵɯ ɫɬɪɢɩɚɯ ɫ ɮɢɤɫɢɪɨɜɚɧɧɵɦɢ ɝɪɚɞɢɟɧɬɚɦɢ pH 4–7 ɢ 3–10
(Bio-Rad). ɂɡɨɷɥɟɤɬɪɨɮɨɤɭɫɢɪɨɜɤɭ ɩɪɨɜɨɞɢɥɢ ɜ ɝɨɪɢɡɨɧɬɚɥɶɧɨɦ ɧɚɩɪɚɜɥɟɧɢɢ ɩɪɢ 20°ɋ, ɤɚɤ ɨɩɢɫɚɧɨ Lázaro ɢ ɫɨɚɜɬ. [55]. ȼɨ ɜɪɟɦɹ ɢɡɨɷɥɟɤɬɪɨɮɨɤɭɫɢɪɨɜɤɢ 2 ɩɨɥɨɫɤɢ ɮɢɥɶɬɪɨɜɚɥɶɧɨɣ ɛɭɦɚɝɢ ɢ ɩɨɥɢɚɤɪɢɥɚɦɢɞɧɵɟ ɫɬɪɢɩɵ ɛɵɥɢ ɩɨɦɟɳɟɧɵ ɦɟɠɞɭ ɷɥɟɤɬɪɨɞɚɦɢ (Electrode
Wicks, Bio-Rad) ɞɥɹ ɭɞɚɥɟɧɢɹ ɫɨɥɟɣ, ɢɡɛɵɬɤɚ ɜɨɞɵ ɢ ɛɟɥɤɨɜ ɫ ɢɡɨɷɥɟɤ-
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ɬɪɢɱɟɫɤɨɣ ɬɨɱɤɨɣ, ɧɚɯɨɞɹɳɟɣɫɹ ɜɧɟ ɩɨɝɪɚɧɢɱɧɵɯ ɡɧɚɱɟɧɢɣ pH ɞɥɹ
ɢɫɩɨɥɶɡɭɸɳɢɯɫɹ ɩɨɥɢɚɤɪɢɥɚɦɢɞɧɵɯ ɫɬɪɢɩɨɜ.
ɉɨ ɨɤɨɧɱɚɧɢɢ ɢɡɨɷɥɟɤɬɪɨɮɨɤɭɫɢɪɨɜɤɢ ɫɬɪɢɩɵ ɜɵɞɟɪɠɢɜɚɥɢ ɜ
ɷɤɜɢɥɢɛɪɢɪɭɸɳɟɦ ɛɭɮɟɪɟ ɢ ɩɪɨɜɨɞɢɥɢ ɷɥɟɤɬɪɨɮɨɪɟɡ ɜɨ ɜɬɨɪɨɦ ɢɡɦɟɪɟɧɢɢ. Ɂɚɬɟɦ ɝɟɥɢ ɨɤɪɚɲɢɜɚɥɢ ɫɟɪɟɛɪɨɦ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɧɚɛɨɪɨɜ
Ampholine PAGplate (Pharmacia Biotech, GE Healthcare) ɜ ɫɨɨɬɜɟɬɫɬɜɢɢ
ɫ ɢɧɫɬɪɭɤɰɢɟɣ ɩɪɨɢɡɜɨɞɢɬɟɥɹ. Ɉɤɪɚɲɟɧɧɵɟ ɝɟɥɢ ɫɤɚɧɢɪɨɜɚɥɢ ɧɚ GS800 ɫɤɚɧɟɪɟ-ɞɟɧɫɢɬɨɦɟɬɪɟ (Bio-Rad) ɢ ɚɧɚɥɢɡɢɪɨɜɚɥɢ ɫ ɩɨɦɨɳɶɸ ɩɪɨɝɪɚɦɦɧɨɝɨ ɩɚɤɟɬɚ PDQUEST 8.0 (Bio-Rad). Ⱦɥɹ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɛɟɥɤɨɜ ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɟ ɩɹɬɧɚ ɜɵɪɟɡɚɥɢ ɢɡ ɝɟɥɹ, ɩɟɪɟɜɚɪɢɜɚɥɢ ɧɚ ɚɜɬɨɦɚɬɟ Ettan Digester (GE Healthcare) ɢ ɩɪɨɜɨɞɢɥɢ ɨɩɪɟɞɟɥɟɧɢɟ ɦɟɬɨɞɨɦ
MALDI-TOF/TOF ɢ ɩɨɢɫɤɨɦ ɫɨɨɬɜɟɬɫɬɜɢɣ ɜ ɛɚɡɟ ɞɚɧɧɵɯ. ȼɤɪɚɬɰɟ,
ɮɪɚɝɦɟɧɬɵ ɝɟɥɹ ɜɨɫɫɬɚɧɚɜɥɢɜɚɥɢ 10 ɦɆ ɞɢɬɢɨɬɪɟɢɬɨɥɨɦ (Sigma Aldrich) ɜ 50 ɦɆ ɛɢɤɚɪɛɨɧɚɬɟ ɚɦɦɨɧɢɹ (Scharlau) ɢ ɚɥɤɢɥɢɪɨɜɚɥɢ 55 ɦɆ
ɢɨɞɨɚɰɟɬɚɦɢɞɨɦ (Sigma Aldrich) in ɜ 50 ɦɆ ɛɢɤɚɪɛɨɧɚɬɟ ɚɦɦɨɧɢɹ.
Ɏɪɚɝɦɟɧɬɵ ɝɟɥɹ ɨɬɦɵɜɚɥɢ ɜ ɜ 50 ɦɆ ɛɢɤɚɪɛɨɧɚɬɟ ɚɦɦɨɧɢɹ, 50% ɦɟɬɚɧɨɥɟ (Scharlau) ɢ ɚɰɟɬɨɧɢɬɪɢɥɟ (Scharlau), ɢ ɜɵɫɭɲɢɜɚɥɟ ɜ Speedvac
(Thermo Fisher). Ɇɨɞɢɮɢɰɢɪɨɜɚɧɧɵɣ Modified ɫɜɢɧɨɣ ɬɪɢɩɫɢɧ (Promega, ɋɒȺ) ɞɨɛɚɜɥɹɥɢ ɤ ɮɪɚɝɦɟɧɬɚɦ ɝɟɥɹ ɜ ɤɨɧɟɱɧɨɣ ɤɨɧɰɟɧɬɪɚɰɢɢ
20 ɧɝ/ɦɤɥ ɜ 20 ɦɆ ɛɢɤɚɪɛɨɧɚɬɟ ɚɦɦɨɧɢɹ ɢ ɩɟɪɟɜɚɪɢɜɚɥɢ ɜ ɬɟɱɟɧɢɟ
ɧɨɱɢ ɩɪɢ 37°C. ɇɚɤɨɧɟɰ, ɞɨɛɚɜɥɹɥɢ 60% ɜɨɞɧɵɣ ɪɚɫɬɜɨɪ ɚɰɟɬɨɧɢɬɪɢɥɚ ɫ 0,1% ɦɭɪɚɜɶɢɧɨɣ ɤɢɫɥɨɬɨɣ (Sigma Aldrich) ɞɥɹ ɩɨɥɧɨɣ ɷɤɫɬɪɚɤɰɢɢ ɩɟɩɬɢɞɨɜ.
ɉɨ ɨɤɨɧɱɚɧɢɢ ɩɟɪɟɜɚɪɢɜɚɧɢɹ ɚɥɢɤɜɨɬɵ ɨɛɪɚɡɰɨɜ ɫɦɟɲɢɜɚɥɢ ɫ
ɚɥɢɤɜɨɬɚɦɢ ɦɚɬɪɢɤɫɚ Į-ɰɢɚɧɨ-4-ɝɢɞɪɨɤɫɢɤɨɪɢɱɧɨɣ ɤɢɫɥɨɬɵ (Sigma
Aldrich) ɜ 50% ɚɰɟɬɨɧɢɬɪɢɥɟ ɫ 0,1% ɬɪɢɮɬɨɪɭɤɫɭɫɧɨɣ ɤɢɫɥɨɬɨɣ.
ɋɦɟɫɶ ɩɨɦɟɳɚɥɢ ɬɨɧɤɢɦ ɫɥɨɟɦ ɧɚ 123´81 ɦɦ Opti-TOF 384 Well
MALDI plate (Applied Biosystems) ɢ ɜɵɫɭɲɢɜɚɥɢ ɩɪɢ ɤɨɦɧɚɬɧɨɣ
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ɬɟɦɩɟɪɚɬɭɪɟ. Ⱦɚɧɧɵɟ MALDI-MS/MS ɩɨɥɭɱɚɥɢ ɚɜɬɨɦɚɬɢɱɟɫɤɢ ɩɪɢ
ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɢ ɧɚ ɚɧɚɥɢɡɚɬɨɪɟ 4800 Plus MALDITOF/TOF
Analyzer
(Applied
Biosystems).
Ɇɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪ
MALDI
(MICROMASS) ɩɨɡɜɨɥɹɟɬ ɨɞɧɨɜɪɟɦɟɧɧɨɟ ɫɱɢɬɵɜɚɧɢɟ ɩɥɚɲɤɢ ɜ ɚɜɬɨɦɚɬɢɱɟɫɤɨɦ ɪɟɠɢɦɟ.
2.15. ɂɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ – MALDI Mass Spec
ɋɩɟɤɬɪɵ ɩɨɥɭɱɚɥɢ ɜ ɪɟɠɢɦɟ ɨɬɪɚɠɟɧɢɹ (reflection mode), ɢɫɩɨɥɶɡɭɹ ɩɪɢɦɟɪɧɨ 150 ɥɚɡɟɪɧɵɯ ɜɵɫɬɪɟɥɨɜ ɩɨ ɜɫɟɣ ɩɥɨɳɚɞɢ ɦɢɲɟɧɢ (ɨɛɪɚɡɰɚ), ɢ ɚɧɚɥɢɡɢɪɨɜɚɥɢ, ɢɫɩɨɥɶɡɭɹ ɩɪɨɝɪɚɦɦɵ ɢ ɛɚɡɭ ɞɚɧɧɵɯ Mascot.
ɉɟɪɟɜɚɪɟɧɧɵɣ ɛɟɥɨɤ ɧɚɧɨɫɢɬɫɹ ɧɚ ɩɥɚɫɬɢɧɭ ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɚ MALDI
(MICROMASS). ɗɬɚ ɩɥɚɫɬɢɧɚ ɢɦɟɟɬ ɬɚɤɭɸ ɠɟ ɤɨɧɮɢɝɭɪɚɰɢɸ, ɤɚɤ ɢ 96ɹɱɟɟɟɱɧɚɹ ɩɥɚɲɤɚ ɞɥɹ ɩɪɹɦɨɣ ɢɧɬɟɪɩɨɥɹɰɢɢ ɢ ɨɩɪɟɞɟɥɟɧɢɹ id.
Ɍɪɢɩɫɢɧ ɩɟɪɟɜɚɪɢɜɚɟɬ ɛɟɥɤɢ ɩɨ ɦɟɫɬɭ ɩɨɥɨɠɟɧɢɹ ɚɪɝɢɧɢɧɚ (R) ɢ
ɥɢɡɢɧɚ (Ʉ), ɩɨɷɬɨɦɭ ɜɟɪɨɹɬɧɨɫɬɶ ɩɪɚɜɢɥɶɧɨɝɨ ɨɩɪɟɞɟɥɟɧɢɹ id ɛɟɥɤɚ ɡɚɜɢɫɢɬ ɨɬ ɧɚɥɢɱɢɹ ɷɬɢɯ ɚɦɢɧɨɤɢɫɥɨɬ ɢ ɫɩɨɫɨɛɧɨɫɬɢ ɮɟɪɦɟɧɬɚ ɪɚɫɩɨɡɧɚɜɚɬɶ ɭɤɚɡɚɧɧɵɟ ɦɟɫɬɚ.
Ɇɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪ ɪɚɡɞɟɥɹɟɬ ɩɟɩɬɢɞɵ ɧɚ ɨɫɧɨɜɟ ɫɨɨɬɧɨɲɟɧɢɹ
ɦɚɫɫɚ/ɡɚɪɹɞ (m/z), ɡɚɩɢɫɵɜɚɟɬ ɫɩɟɤɬɪ ɞɥɹ ɤɚɠɞɨɝɨ ɨɛɪɚɡɰɚ ɢ ɢɳɟɬ ɟɝɨ
ɫɨɨɬɜɟɬɫɬɜɢɟ ɛɚɡɟ ɞɚɧɧɵɯ (Human, SwissProt). ȼɟɪɨɹɬɧɨɫɬɶ ɷɬɨɝɨ ɫɨɨɬɜɟɬɫɬɜɢɹ ɡɚɜɢɫɢɬ ɨɬ ɩɪɢɫɭɬɫɬɜɢɹ/ɨɬɫɭɬɫɬɜɢɹ ɩɟɩɬɢɞɚ ɜ ɫɩɟɤɬɪɟ ɢ ɬ.ɧ.
ɩɟɪɟɤɪɵɬɢɹ (ɩɪɢɫɭɬɫɬɜɢɹ ɟɝɨ ɜ ɛɟɥɤɟ). ɂɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ, ɬɚɤɢɦ
ɨɛɪɚɡɨɦ, ɪɚɫɫɦɚɬɪɢɜɚɟɬɫɹ ɤɚɤ ɪɟɡɭɥɶɬɚɬ ɤɨɦɩɶɸɬɟɪɧɨɝɨ ɩɨɢɫɤɚ ɩɨ ɛɚɡɚɦ ɞɚɧɧɵɯ ɨ ɫɟɤɜɟɧɢɪɨɜɚɧɧɵɯ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɹɯ (ɧɚɩɪɢɦɟɪ,
NCBI) ɢ ɪɚɫɱɟɬɟ ɩɪɨɰɟɧɬɚ ɫɨɜɩɚɞɟɧɢɹ ɜɵɹɜɥɟɧɧɵɯ ɦɚɫɫ ɬɪɢɩɬɢɱɟɫɤɢɯ
ɩɟɩɬɢɞɨɜ ɫ ɚɦɢɧɨɤɢɫɥɨɬɧɨɣ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɶɸ ɫɨɨɬɜɟɬɫɬɜɭɸɳɟɝɨ
ɛɟɥɤɚ (% ɩɟɪɟɤɪɵɬɢɹ).
54
2.16. Ɉɛɴɟɞɢɧɟɧɢɟ ɞɚɧɧɵɯ, ɩɨɥɭɱɟɧɧɵɯ ɧɚ ɪɚɡɧɵɯ ɷɬɚɩɚɯ ɚɧɚɥɢɡɚ
Ⱦɥɹ ɤɨɧɬɪɨɥɹ ɡɚ ɯɨɞɨɦ ɩɪɨɰɟɞɭɪɵ ɚɧɚɥɢɡɚ ɢɫɩɨɥɶɡɨɜɚɥɚɫɶ ɫɩɟɰɢɚɥɶɧɚɹ ɪɚɛɨɱɚɹ ɬɟɬɪɚɞɶ. ȼ ɧɟɟ ɜɧɨɫɢɥɢɫɶ ɪɟɡɭɥɶɬɢɪɭɸɳɢɟ ɞɚɧɧɵɟ ɤɚɠɞɨɣ ɫɬɚɞɢɢ ɚɧɚɥɢɡɚ, ɤɨɬɨɪɵɟ ɡɚɬɟɦ ɨɛɴɟɞɢɧɹɥɢɫɶ ɞɥɹ ɩɨɥɭɱɟɧɢɹ ɡɧɚɱɢɦɨɝɨ ɢɬɨɝɚ, ɜ ɧɚɲɟɦ ɫɥɭɱɚɟ – id ɛɟɥɤɚ, ɫɨɨɬɜɟɬɫɬɜɭɸɳɟɝɨ ɛɟɥɤɨɜɨɦɭ ɩɹɬɧɭ ɧɚ ɛɟɥɤɨɜɨɦ ɝɟɥɟ (ɪɢɫ. 2.4). ɇɨɦɟɪ ɩɹɬɧɚ ɦɨɠɟɬ ɛɵɬɶ ɢɫɩɨɥɶɡɨɜɚɧ ɞɥɹ ɫɜɹɡɢ id ɫ ɞɪɭɝɢɦɢ ɷɬɚɩɚɦɢ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ. ɇɚ
ɪɢɫ. 2.5 ɩɪɟɞɫɬɚɜɥɟɧ ɩɪɢɦɟɪ ɡɚɩɢɫɢ ɨ ɜɵɪɟɡɚɧɢɢ ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ.
ɉɪɟɞɫɬɚɜɥɟɧɧɨɟ ɜɵɲɟ ɫɨɨɛɳɟɧɢɟ ɝɟɧɟɪɢɪɭɟɬɫɹ ɞɥɹ ɤɚɠɞɨɝɨ ɝɟɥɹ
ɢ ɩɪɟɞɫɬɚɜɥɹɟɬ ɫɨɛɨɣ ɜɚɠɧɭɸ ɫɜɹɡɶ ɦɟɠɞɭ ɝɟɥɟɜɵɦ ɫɬɨɥɛɢɤɨɦ, ɧɚɩɪɚɜɥɹɟɦɵɦ ɜ ɪɨɛɨɬ ɩɟɪɟɜɚɪɢɜɚɧɢɹ ɛɟɥɤɚ, ɢ ɛɟɥɤɨɜɵɦ ɩɹɬɧɨɦ ɧɚ ɝɟɥɟ.
Ʉɚɠɞɵɣ ɝɟɥɶ ɩɨɥɭɱɚɥ ɫɨɛɫɬɜɟɧɧɨɟ ɧɚɢɦɟɧɨɜɚɧɢɟ, ɚ ɩɪɢɜɟɞɟɧɧɵɣ
ɩɪɢɦɟɪ ɫɨɨɬɜɟɬɫɬɜɭɟɬ 664 ɢɡɜɥɟɱɟɧɧɵɦ ɛɟɥɤɚɦ.
Ɋɢɫ. 2.4. Ȼɟɥɤɨɜɵɣ ɝɟɥɶ – ɤɚɠɞɨɟ ɛɟɥɤɨɜɨɟ ɩɹɬɧɨ ɧɚ ɢɡɨɛɪɚɠɟɧɢɢ ɝɟɥɹ
ɢɦɟɟɬ ɡɧɚɱɟɧɢɟ id
55
Ɋɢɫ. 2.5. ɋɨɨɛɳɟɧɢɟ (ɡɚɩɢɫɶ) ɨ ɜɵɪɟɡɚɧɢɢ ɛɟɥɤɨɜ – ɤɚɠɞɨɟ ɛɟɥɤɨɜɨɟ
ɩɹɬɧɨ ɫɨɨɬɜɟɬɫɬɜɭɟɬ ɧɨɦɟɪɭ ɹɱɟɣɤɢ
2.17. ɂɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ
ɇɚ ɪɢɫ. 2.6 ɩɪɟɞɫɬɚɜɥɟɧ ɩɪɢɦɟɪ ɡɚɩɢɫɢ (ɪɚɫɩɟɱɚɬɤɢ) ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɯ ɛɟɥɤɨɜ. ɍɪɨɜɟɧɶ ɜɟɪɨɹɬɧɨɫɬɢ ɩɨɡɜɨɥɹɟɬ ɨɰɟɧɢɬɶ ɨɬɧɨɫɢɬɟɥɶɧɭɸ ɧɚɞɟɠɧɨɫɬɶ ɩɨɥɭɱɟɧɧɨɣ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɛɟɥɤɚ. Ⱦɚɥɟɟ
ɛɟɥɨɤ ɦɨɠɟɬ ɚɧɚɥɢɡɢɪɨɜɚɬɶɫɹ ɫ ɩɨɦɨɳɶɸ ɛɚɡɵ ɞɚɧɧɵɯ SwissProt,
ɤɨɬɨɪɚɹ ɩɨɡɜɨɥɹɟɬ ɭɬɨɱɧɢɬɶ ɧɟ ɬɨɥɶɤɨ ɟɝɨ ɮɭɧɤɰɢɢ, ɧɨ ɢ ɤɨɦɩɚɪɬɦɟɧɬɚɥɢɡɚɰɢɸ. ȼ ɤɨɧɟɱɧɨɦ ɫɱɟɬɟ, ɤɚɪɬɢɪɨɜɚɧɢɟ ɝɟɧɨɦɚ ɨɛɟɫɩɟɱɢɜɚɟɬ ɧɟɨɛɯɨɞɢɦɭɸ ɢɧɮɨɪɦɚɰɢɸ ɞɥɹ ɞɚɥɶɧɟɣɲɢɯ ɫɪɚɜɧɢɬɟɥɶɧɵɯ ɢɫɫɥɟɞɨɜɚɧɢɣ.
56
Ɋɢɫ. 2.6. ɉɪɢɦɟɪ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɛɟɥɤɨɜ – ɤɚɠɞɨɦɭ ɧɨɦɟɪɭ ɹɱɟɣɤɢ
ɫɨɨɬɜɟɬɫɬɜɭɟɬ ɛɟɥɨɤ ɢ ɜɟɪɨɹɬɧɨɫɬɶ ɟɝɨ ɩɪɚɜɢɥɶɧɨɣ ɢɞɟɧɬɢɮɢɤɚɰɢɢ
Ⱦɥɹ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɛɟɥɤɨɜ ɜ ɤɚɪɞɢɨɩɪɟɩɚɪɚɬɚɯ ɫɩɟɤɬɪɵ ɩɨɝɥɨɳɟɧɢɹ ɡɚɯɜɚɬɵɜɚɥɢ ɜ ɪɟɠɢɦɟ ɩɨɥɨɠɢɬɟɥɶɧɨ ɡɚɪɹɠɟɧɧɵɯ ɢɨɧɨɜ, ɢɫɩɨɥɶɡɭɹ 355-ɧɦ Nd:YAG ɥɚɡɟɪ ɫ ɱɚɫɬɨɬɨɣ 200 Ƚɰ, ɢ ɩɨɥɭɱɚɥɢ ɨɬ 100
ɞɨ 2000 ɢɧɞɢɜɢɞɭɚɥɶɧɵɯ ɫɩɟɤɬɪɨɜ. Ⱦɥɹ ɚɧɚɥɢɡɚ ɮɪɚɝɦɟɧɬɨɜ ɢɨɧɨɜ ɜ
ɬɚɧɞɟɦɟ TOF/TOF, ɢɨɧɵ-ɩɪɟɞɲɟɫɬɜɟɧɧɢɤɢ ɭɫɤɨɪɹɥɢɫɶ ɞɨ 8 ɤȼ ɢ ɨɬɛɢɪɚɥɢɫɶ ɜ ɩɨɪɬɭ ɜɯɨɞɚ ɢɨɧɨɜ. Ɏɪɚɝɦɟɧɬɵ, ɜɨɡɧɢɤɚɸɳɢɟ ɜ ɪɟɡɭɥɶɬɚɬɟ
ɫɬɨɥɤɧɨɜɟɧɢɹ ɦɟɠɞɭ ɩɪɟɞɲɟɫɬɜɟɧɧɢɤɚɦɢ ɢ ɜɨɡɞɭɯɨɦ ɜ ɤɨɥɥɢɡɢɨɧɧɨɣ
ɤɚɦɟɪɟ, ɛɵɥɢ ɭɫɤɨɪɟɧɵ ɞɨ 15 ɤȼ ɜ ɢɫɬɨɱɧɢɤɟ 2, ɢ ɢɯ ɦɚɫɫɵ ɛɵɥɢ ɩɪɨɚɧɚɥɢɡɢɪɨɜɚɧɵ ɩɨɫɥɟ ɩɪɨɯɨɠɞɟɧɢɹ ɨɬɪɚɠɚɬɟɥɹ ɢɨɧɨɜ. Ⱦɚɧɧɵɟ ɨ ɦɚɫɫɚɯ ɛɵɥɢ ɩɪɨɚɧɚɥɢɡɢɪɨɜɚɧɵ ɚɜɬɨɦɚɬɢɱɟɫɤɢ ɫ ɩɨɦɨɳɶɸ ɩɪɨɝɪɚɦɦɧɨɝɨ
ɩɚɤɟɬɚ 4000 Series Explorer ɜɟɪɫɢɢ 3.5.3 (Applied Biosystems). ȼɧɭɬɪɟɧɧɹɹ ɤɚɥɢɛɪɨɜɤɚ MALDI-TOF ɩɪɨɜɨɞɢɥɚɫɶ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ 2 ɢɨɧɨɜ ɚɜɬɨɥɢɡɚ ɬɪɢɩɫɢɧɚ (m/z=842,510 ɢ m/z=2211.105, ɫɨɨɬɜɟɬɫɬɜɟɧɧɨ).
Ʉɚɥɢɛɪɨɜɤɚ MALDI-MS/MS ɩɪɨɜɨɞɢɥɚɫɶ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɢɨɧɧɵɯ
ɫɩɟɤɬɪɨɜ ɮɪɚɝɦɟɧɬɨɜ Glu1-ɮɢɛɪɢɧɨɩɟɩɬɢɞɚ B (4800 MALDI/TOFTOF, Applied Biosystems). Ⱦɚɧɧɵɟ MALDI-MS ɢ MS/MS ɛɵɥɢ ɨɛɴɟ-
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ɞɢɧɟɧɵ ɫ ɩɨɦɨɳɶɸ ɩɪɨɝɪɚɦɦɵ GPS Explorer ɜɟɪɫɢɢ 3.6, ɤɨɬɨɪɚɹ ɩɨɡɜɨɥɹɟɬ ɩɪɨɜɨɞɢɬɶ ɧɟɪɟɡɟɪɜɢɪɭɸɳɢɣ ɩɨɢɫɤ ɜ ɛɚɡɟ ɞɚɧɧɵɯ ɛɟɥɤɨɜ
NCBI (ɜɟɪɫɢɹ 20080225) ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɩɪɨɝɪɚɦɦɵ Mascot ɜɟɪɫɢɢ
2.1 (Matrix science), ɩɪɢ ɞɨɩɭɫɤɟ ɨɲɢɛɤɢ ɨɩɪɟɞɟɥɟɧɢɹ ɦɚɫɫɨɜɨɣ ɞɨɥɢ
ɞɨ 50 ppm ɢ ɨɞɧɨɝɨ ɩɪɨɩɭɫɤɚ ɪɚɫɳɟɩɥɟɧɢɹ.
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3. ɉɈɅɍɑȿɇɇɕȿ ɊȿɁɍɅɖɌȺɌɕ
3.1 ȼɥɢɹɧɢɟ ɩɚɪɚɬɢɪɟɨɢɞɧɨɝɨ ɝɨɪɦɨɧɚ ɧɚ ɨɫɬɟɨɛɥɚɫɬɵ
ɂɡɜɟɫɬɧɨ, ɱɬɨ ɤɨɦɩɨɧɟɧɬɵ ɬɚɤ ɧɚɡɵɜɚɟɦɵɯ «ɧɢɲ» ɋɄ [108] ɨɩɪɟɞɟɥɹɸɬ ɢɯ ɮɭɧɤɰɢɨɧɚɥɶɧɨɟ ɫɨɫɬɨɹɧɢɟ ɢ, ɜ ɱɚɫɬɧɨɫɬɢ, ɩɪɟɩɹɬɫɬɜɭɸɬ
ɩɨɬɟɪɟ ɜɵɫɨɤɨɝɨ ɩɪɨɥɢɮɟɪɚɬɢɜɧɨɝɨ ɩɨɬɟɧɰɢɚɥɚ. ɍɫɬɚɧɨɜɥɟɧɨ, ɱɬɨ
ɜɚɠɧɵɦ ɫɬɪɭɤɬɭɪɧɵɦ ɷɥɟɦɟɧɬɨɦ ɧɢɲ ɹɜɥɹɸɬɫɹ ɨɫɬɟɨɛɥɚɫɬɵ, ɤɨɥɢɱɟɫɬɜɨ ɢ ɚɤɬɢɜɚɰɢɸ ɤɨɬɨɪɵɯ ɦɨɠɧɨ ɪɟɝɭɥɢɪɨɜɚɬɶ ɫ ɩɨɦɨɳɶɸ ɩɚɪɚɬɢɪɟɨɢɞɧɨɝɨ ɝɨɪɦɨɧɚ (ɉɌȽ). Ɉɫɬɟɨɛɥɚɫɬɵ ɫɬɢɦɭɥɢɪɭɸɬɫɹ ɉɌȽ ɢɥɢ ɥɨɤɚɥɶɧɨ ɨɛɪɚɡɭɸɳɢɦɫɹ ɫɜɹɡɚɧɧɵɦ ɫ ɧɢɦ ɛɟɥɤɨɦ (PTHrP) ɱɟɪɟɡ ɪɟɰɟɩɬɨɪ (PPR) ɤ ɧɢɦ [23, 24].
ȼ ɪɹɞɟ ɷɤɫɩɟɪɢɦɟɧɬɨɜ ɩɨɤɚɡɚɧɨ, ɱɬɨ ɩɨɫɥɟ ɢɧɴɟɤɰɢɣ ɧɟɛɨɥɶɲɢɯ ɤɨɥɢɱɟɫɬɜ ɉɌȽ, ɫɨɩɨɫɬɚɜɢɦɵɯ ɫ ɢɫɩɨɥɶɡɭɟɦɵɦɢ ɞɥɹ ɥɟɱɟɧɢɹ
ɨɫɬɟɨɩɨɪɨɡɚ, ɱɢɫɥɨ ɫɚɦɵɯ ɪɚɧɧɢɯ ɩɨɥɢɩɨɬɟɧɬɧɵɯ ȽɋɄ ɭɜɟɥɢɱɢɜɚɟɬɫɹ ɜ 2 ɪɚɡɚ, ɚ ɦɵɲɢ, ɜɨɫɫɬɚɧɚɜɥɢɜɚɸɳɢɟɫɹ ɩɨɫɥɟ ɥɟɬɚɥɶɧɨɝɨ ɨɛɥɭɱɟɧɢɹ ɩɨɞ ɞɟɣɫɬɜɢɟɦ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ, ɨɛɪɚɛɨɬɚɧɧɨɝɨ ɉɌȽ, ɥɭɱɲɟ
ɜɵɠɢɜɚɸɬ [26].
ɗɬɨɬ ɷɮɮɟɤɬ, ɜɢɞɢɦɨ, ɫɜɹɡɚɧ ɫ ɩɨɜɵɲɟɧɢɟɦ ɷɤɫɩɪɟɫɫɢɢ Jagged
1 – ɥɢɝɚɧɞɚ, ɥɨɤɚɥɢɡɨɜɚɧɧɨɝɨ ɧɚ ɩɨɜɟɪɯɧɨɫɬɢ ɨɫɬɟɨɛɥɚɫɬɨɜ, ɤɨɬɨɪɵɣ
ɜɡɚɢɦɨɞɟɣɫɬɜɭɟɬ ɫ ɪɟɰɟɩɬɨɪɨɦ Notch 1, ɷɤɫɩɪɟɫɫɢɪɨɜɚɧɧɵɦ ɧɚ ɩɨɜɟɪɯɧɨɫɬɢ ȽɋɄ [49, 102]. Ɍɚɤɨɟ ɜɡɚɢɦɨɞɟɣɫɬɜɢɟ ɫɬɢɦɭɥɢɪɭɟɬ ɩɪɨɥɢɮɟɪɚɰɢɸ ȽɋɄ.
ȼ ɬɨ ɠɟ ɜɪɟɦɹ ɦɨɥɟɤɭɥɹɪɧɵɟ ɦɟɯɚɧɢɡɦɵ ɜɡɚɢɦɨɞɟɣɫɬɜɢɹ ɉɌȽ ɢ
ɨɫɬɟɨɛɥɚɫɬɨɜ ɨɫɬɚɸɬɫɹ ɦɚɥɨɢɡɭɱɟɧɧɵɦɢ, ɱɬɨ ɧɟ ɩɨɡɜɨɥɹɟɬ ɜ ɞɨɥɠɧɨɣ
ɦɟɪɟ ɢɧɬɟɪɩɪɟɬɢɪɨɜɚɬɶ ɜɥɢɹɧɢɟ ɩɨɫɥɟɞɧɢɯ ɧɚ ȽɋɄ.
ȼ ɷɬɨɣ ɫɜɹɡɢ ɰɟɥɶɸ ɩɟɪɜɨɣ ɱɚɫɬɢ ɧɚɲɟɝɨ ɢɫɫɥɟɞɨɜɚɧɢɹ ɹɜɢɥɨɫɶ ɜɵɹɜɥɟɧɢɟ ɛɟɥɤɨɜ ɨɫɬɟɨɛɥɚɫɬɨɜ, ɢɡɦɟɧɹɸɳɢɯɫɹ ɩɨɞ ɞɟɣɫɬɜɢɟɦ ɝɨɪɦɨɧɚ, ɹɜ-
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ɥɹɸɳɟɝɨɫɹ, ɩɨ ɫɭɬɢ ɞɟɥɚ, ɡɚɩɭɫɤɚɸɳɢɦ ɡɜɟɧɨɦ ɜɡɚɢɦɨɞɟɣɫɬɜɢɹ ɦɟɠɞɭ
ɨɫɬɟɨɛɥɚɫɬɚɦɢ ɤɚɤ ɤɨɦɩɨɧɟɧɬɚɦɢ ɧɢɲɢ, ɢ ɧɚɯɨɞɹɳɢɦɢɫɹ ɜ ɧɟɣ ȽɋɄ.
ȼ ɷɤɫɩɟɪɢɦɟɧɬɚɯ ɢɫɩɨɥɶɡɨɜɚɧɚ ɤɥɟɬɨɱɧɚɹ ɥɢɧɢɹ ɨɫɬɟɨɛɥɚɫɬɩɨɞɨɛɧɨɣ ɨɫɬɟɨɫɚɪɤɨɦɵ MG63 ɱɟɥɨɜɟɤɚ ɜ ɤɚɱɟɫɬɜɟ ɦɨɞɟɥɢ ɞɥɹ ɢɫɫɥɟɞɨɜɚɧɢɹ ɷɮɮɟɤɬɨɜ ɉɌȽ (ɮɪɚɝɦɟɧɬ ɱɟɥɨɜɟɱɟɫɤɨɝɨ ɉɌȽ ɫ ɚɦɢɧɨɤɢɫɥɨɬɚɦɢ
1–34). Ʉɥɟɬɤɢ ɤɭɥɶɬɢɜɢɪɨɜɚɥɢ ɜ ɫɪɟɞɟ Dulbecco"s Modified Eagle
(DɆȿɆ), ɫɨɞɟɪɠɚɳɟɣ 10% ɷɦɛɪɢɨɧɚɥɶɧɭɸ ɛɵɱɶɸ ɫɵɜɨɪɨɬɤɭ, 1%
L-ɝɥɭɬɚɦɢɧ, 1% ɚɧɬɢɛɢɨɬɢɤ-ɚɧɬɢɦɢɤɨɬɢɤ ɢ 1% ɡɚɦɟɧɢɦɵɯ ɚɦɢɧɨɤɢɫɥɨɬ ɜ 5% ɋɈ2 ɢɧɤɭɛɚɬɨɪɟ ɩɪɢ ɬɟɦɩɟɪɚɬɭɪɟ 370ɋ. ɉɪɢ 70%-ɨɣ ɤɨɧɮɥɭɟɧɬɧɨɫɬɢ ɤɥɟɬɤɢ ɛɵɥɢ ɩɟɪɟɧɟɫɟɧɵ ɜ «ɨɛɟɞɧɟɧɧɭɸ» ɫɪɟɞɭ 0,1% ɎȻɋ
(ɮɟɬɚɥɶɧɨɣ ɛɵɱɶɟɣ ɫɵɜɨɪɨɬɤɢ) ɧɚ 48 ɱɚɫɨɜ ɞɥɹ ɫɢɧɯɪɨɧɢɡɚɰɢɢ ɜ ɮɚɡɟ
G1 ɩɟɪɟɞ ɞɨɛɚɜɥɟɧɢɟɦ 10–7 Ɇ ɉɌȽ ɢɥɢ ɤɨɧɬɪɨɥɶɧɨɝɨ ɫɨɥɟɜɨɝɨ ɪɚɫɬɜɨɪɚ. FACS ɢɫɩɨɥɶɡɨɜɚɥɫɹ ɞɥɹ ɩɨɞɬɜɟɪɠɞɟɧɢɹ G1 ɫɢɧɯɪɨɧɢɡɚɰɢɢ ɨɛɟɞɧɟɧɧɵɯ ɫɵɜɨɪɨɬɤɨɣ ɤɥɟɬɨɤ MG63.
Ʉɥɟɬɤɢ, ɡɚɮɢɤɫɢɪɨɜɚɧɧɵɟ 70% ɷɬɚɧɨɥɨɦ, ɞɜɚɠɞɵ ɩɪɨɦɵɜɚɥɢ
ɮɨɫɮɚɬ-ɰɢɬɪɚɬɧɵɦ ɛɭɮɟɪɧɵɦ ɪɚɫɬɜɨɪɨɦ ɢ ɪɟɫɭɫɩɟɧɞɢɪɨɜɚɥɢ ɜ 50
ɦɤɥ 100 ɦɤɝ/ɦɥ ɊɇɄɚɡɵ-Ⱥ ɢ 300 ɦɤɥ 50 ɦɤɝ/ɦɥ ɩɪɨɩɢɞɢɭɦ-ɢɨɞɢɞɚ ɢ
ɢɧɤɭɛɢɪɨɜɚɥɢ ɩɪɢ ɤɨɦɧɚɬɧɨɣ ɬɟɦɩɟɪɚɬɭɪɟ ɜ ɬɟɱɟɧɢɟ 30 ɦɢɧ.
Ɉɛɳɟɟ ɤɨɥɢɱɟɫɬɜɨ ɤɥɟɬɨɤ (10 000 ɧɚ ɩɨɩɭɥɹɰɢɸ) ɚɧɚɥɢɡɢɪɨɜɚɥɨɫɶ ɫ ɩɨɦɨɳɶɸ FACSvCalibur ɩɪɨɬɨɱɧɨɝɨ ɰɢɬɨɦɟɬɪɚ (Becton Dickenson) ɢ ɦɚɪɤɟɪɵ ɤɥɟɬɨɱɧɨɝɨ ɰɢɤɥɚ ɢɫɩɨɥɶɡɨɜɚɥɢɫɶ ɞɥɹ ɩɨɫɬɪɨɟɧɢɹ
ɝɢɫɬɨɝɪɚɦɦ ɫɨɞɟɪɠɚɧɢɹ ȾɇɄ ɫ ɩɨɦɨɳɶɸ ɤɨɦɩɶɸɬɟɪɧɨɝɨ ɩɚɤɟɬɚ
CellQuest Pro Software, ɩɨɡɜɨɥɹɸɳɟɝɨ ɨɰɟɧɢɜɚɬɶ ɩɪɨɩɨɪɰɢɢ ɤɥɟɬɨɤ
ɜ G0/G1, S ɢ G2/M ɮɚɡɚɯ ɤɥɟɬɨɱɧɨɝɨ ɰɢɤɥɚ.
FACS-ɚɧɚɥɢɡ ɢɫɩɨɥɶɡɨɜɚɥɫɹ ɬɚɤɠɟ ɞɥɹ ɨɩɪɟɞɟɥɟɧɢɹ, ɢɧɞɭɰɢɪɭɟɬ
ɥɢ ɛɨɥɟɟ ɞɥɢɬɟɥɶɧɨɟ «ɝɨɥɨɞɚɧɢɟ» ɚɩɨɩɬɨɡ ɜ ɤɨɧɬɪɨɥɶɧɵɯ ɤɥɟɬɤɚɯ (ɱɟɪɟɡ
32 ɱɚɫɚ), ɢ ɫɬɢɦɭɥɢɪɭɟɬ ɥɢ ɨɛɪɚɛɨɬɤɚ ɉɌȽ ɝɨɥɨɞɚɸɳɢɯ MG63 ɤɥɟɬɤɢ
(ɬɚɤɠɟ ɱɟɪɟɡ 32 ɱɚɫɚ) ɤ ɧɨɜɨɦɭ ɜɫɬɭɩɥɟɧɢɸ ɜ ɤɥɟɬɨɱɧɵɣ ɰɢɤɥ.
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ȼ ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɩɨɥɭɱɟɧɧɵɦɢ ɪɟɡɭɥɶɬɚɬɚɦɢ, 48-ɱɚɫɨɜɨɟ ɝɨɥɨɞɚɧɢɟ ɛɵɥɨ ɞɨɫɬɚɬɨɱɧɵɦ ɞɥɹ ɫɢɧɯɪɨɧɢɡɚɰɢɢ MG63 ɤɥɟɬɨɤ ɜ ɫɬɚɞɢɢ G0/G1
ɤɥɟɬɨɱɧɨɝɨ ɰɢɤɥɚ (ɩɪɢɛɥɢɡɢɬɟɥɶɧɨ 90% ɤɥɟɬɨɤ ɧɚɯɨɞɢɥɢɫɶ ɜ ɫɨɫɬɨɹɧɢɢ
ɮɚɡɵ G0/G1). Ʉɚɤ ɩɨɤɚɡɚɧɨ ɫ ɩɨɦɨɳɶɸ FACS, ɞɨɩɨɥɧɢɬɟɥɶɧɵɟ 32 ɱɚɫɚ
ɫɵɜɨɪɨɬɨɱɧɨɝɨ ɝɨɥɨɞɚɧɢɹ ɜ ɤɨɧɬɪɨɥɶɧɨɣ ɩɨɩɭɥɹɰɢɢ, ɨɛɪɚɛɨɬɚɧɧɨɣ ɫɨɥɟɜɵɦ ɪɚɫɬɜɨɪɨɦ, ɧɟ ɢɧɞɭɰɢɪɨɜɚɥɢ ɚɩɨɩɬɨɡ ɜ MG63 ɤɥɟɬɤɚɯ, ɚ ɤɥɟɬɤɢ,
ɨɛɪɚɛɨɬɚɧɧɵɟ ɉɌȽ ɜ ɬɟɱɟɧɢɟ 32 ɱɚɫɨɜ, ɧɟ ɛɵɥɢ ɫɬɢɦɭɥɢɪɨɜɚɧɵ ɤ ɩɨɜɬɨɪɧɨɦɭ ɜɫɬɭɩɥɟɧɢɸ ɜ ɤɥɟɬɨɱɧɵɣ ɰɢɤɥ ɢɡ ɫɬɚɞɢɢ ɩɨɤɨɹ.
ɉɪɢɦɟɪɧɨ 3×106 ɤɥɟɬɨɤ ɛɵɥɢ ɜɡɹɬɵ ɱɟɪɟɡ 4, 8, ɢ 32 ɱɚɫɚ ɩɨɫɥɟ
ɜɡɚɢɦɨɞɟɣɫɬɜɢɹ ɫ ɉɌȽ ɢ ɢɡ ɤɨɧɬɪɨɥɹ ɢ ɯɪɚɧɢɥɢɫɶ ɩɪɢ –80°C.
ɇɚɛɨɪ Clean-Up ɢɫɩɨɥɶɡɨɜɚɥɫɹ ɞɥɹ ɭɞɚɥɟɧɢɹ ɩɪɢɦɟɫɟɣ ɩɟɪɟɞ ɡɚɝɪɭɡɤɨɣ ɧɚ 2D ɜ ɩɟɪɜɨɦ ɧɚɩɪɚɜɥɟɧɢɢ. Ʉɨɧɰɟɧɬɪɚɰɢɹ ɛɟɥɤɚ ɤɨɥɢɱɟɫɬɜɟɧɧɨ ɨɩɪɟɞɟɥɹɥɚɫɶ ɫ ɩɨɦɨɳɶɸ ɧɚɛɨɪɚ ȼɋȺ. Ʌɢɡɚɬɵ (50 ɦɤɝ ɛɟɥɤɚ)
ɧɚɧɨɫɢɥɢɫɶ ɧɚ ɨɛɟɡɜɨɠɟɧɧɵɟ IPG-ɫɬɪɢɩɵ ɫ ɩɨɦɨɳɶɸ ɩɪɢɛɨɪɚ IPGphor II (GE- Healthcare).
Ɋɟɡɭɥɶɬɚɬɵ, ɯɚɪɚɤɬɟɪɢɡɭɸɳɢɟ ɢɞɟɧɬɢɮɢɤɚɰɢɸ ɛɟɥɤɨɜ ɢ ɢɯ ɩɨɜɟɞɟɧɢɟ ɤɚɤ ɫɥɟɞɫɬɜɢɟ ɜɡɚɢɦɨɞɟɣɫɬɜɢɹ ɫ ɉɌȽ ɜ ɬɟɱɟɧɢɟ 4, 8 ɢ 32 ɱɚɫɨɜ,
ɩɪɟɞɫɬɚɜɥɟɧɵ ɜ ɬɚɛɥ. 3.1. ȼ ɫɨɜɨɤɭɩɧɨɫɬɢ ɫ ɞɚɧɧɵɦɢ ɩɨ ɨɤɪɚɲɢɜɚɧɢɸ
ɤɥɟɬɨɤ, ɨɧɢ ɫɜɢɞɟɬɟɥɶɫɬɜɭɸɬ ɨ ɫɥɟɞɭɸɳɟɦ.
ɉɌȽ ɫɬɢɦɭɥɢɪɭɟɬ ɜɵɠɢɜɚɧɢɟ ɧɚɯɨɞɹɳɢɯɫɹ ɜ ɫɬɚɞɢɢ ɩɨɤɨɹ (ɥɢɲɟɧɧɵɯ ɩɢɬɚɧɢɹ) ɨɫɬɟɨɛɥɚɫɬɨɜ. ɂɯ ɨɬɦɢɪɚɧɢɟ, ɚɫɫɨɰɢɢɪɨɜɚɧɧɨɟ ɫ ɮɚɤɬɨɪɨɦ ɬɪɚɧɫɤɪɢɩɰɢɢ 1, ɫɧɢɠɚɟɬɫɹ ɜ 4 ɪɚɡɚ ɩɨɫɥɟ ɨɛɪɚɛɨɬɤɢ ɉɌȽ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɤɨɧɬɪɨɥɟɦ.
ȼɫɟɝɨ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɨ 15 ɛɟɥɤɨɜ, ɤɨɥɢɱɟɫɬɜɨ ɤɨɬɨɪɵɯ ɩɪɟɬɟɪɩɟɜɚɟɬ ɢɡɦɟɧɟɧɢɟ ɩɪɢ ɞɟɣɫɬɜɢɢ ɉɌȽ ɧɚ ɨɫɬɟɨɛɥɚɫɬɵ, ɩɪɢɱɟɦ ɤɚɠɞɨɟ ɭɞɥɢɧɟɧɢɟ ɜɪɟɦɟɧɢ ɜɥɢɹɧɢɹ ɉɌȽ ɧɚ ɨɫɬɟɨɛɥɚɫɬɵ ɩɪɢɜɨɞɢɬ ɤ
ɨɛɧɚɪɭɠɟɧɢɸ ɧɨɜɵɯ ɛɟɥɤɨɜ, ɫɨɞɟɪɠɚɧɢɟ ɤɨɬɨɪɵɯ ɭɜɟɥɢɱɢɜɚɟɬɫɹ
ɢɥɢ ɭɦɟɧɶɲɚɟɬɫɹ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɤɨɧɬɪɨɥɟɦ.
61
ɗɬɢ ɞɚɧɧɵɟ ɞɨɩɨɥɧɹɸɬ ɪɚɧɟɟ ɨɩɭɛɥɢɤɨɜɚɧɧɵɟ ɫɜɟɞɟɧɢɹ ɩɨ ɢɫɫɥɟɞɨɜɚɧɢɸ ɩɪɨɬɟɨɦɚ ɨɫɬɟɨɛɥɚɫɬɨɜ ɢɡ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɦɵɲɟɣ [4, 49].
Ɍɚɛɥɢɰɚ 3.1. ɂɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟ ɫ ɩɨɦɨɳɶɸ ɩɪɨɬɟɨɦɢɤɢ ɛɟɥɤɢ
ɨɫɬɟɨɛɥɚɫɬɨɜ, ɤɨɥɢɱɟɫɬɜɨ ɤɨɬɨɪɵɯ ɢɡɦɟɧɹɟɬɫɹ ɩɨɫɥɟ ɜɡɚɢɦɨɞɟɣɫɬɜɢɹ
ɤɥɟɬɨɤ ɫ ɉɌȽ ɜ ɬɟɱɟɧɢɟ ɪɚɡɧɵɯ ɩɟɪɢɨɞɨɜ ɜɪɟɦɟɧɢ
ɉɪɨɞɨɥɠɢɂɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟ
ɂɡɦɟɧɟɧɢɟ
ɬɟɥɶɧɨɫɬɶ ɜɡɚɢɛɟɥɤɢ
ɤɨɥɢɱɟɫɬɜɚ ɛɟɥɤɚ
ɦɨɞɟɣɫɬɜɢɹ (ɱɚɫ)
Ribosomal protein S6 kinase 3-ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ
Microtubule-associated pro2-ɤɪɚɬɧɨɟ ɭɜɟɥɢɱɟɧɢɟ
tein tau
4
Putative NFkB activating
4-ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ
protein
Endoplasmic-reticulum20-ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ
lumenal protein 28
Ran-specific GTPase9-ɤɪɚɬɧɨɟ ɭɜɟɥɢɱɟɧɢɟ
activating protein
Fibroblast growth factor-20 5-ɤɪɚɬɧɨɟ ɭɜɟɥɢɱɟɧɢɟ
8
Death receptor 5
4-ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ
Putative espin
3-ɤɪɚɬɧɨɟ ɭɜɟɥɢɱɟɧɢɟ
Novel protein (MGC26989) 2- ɤɪɚɬɧɨɟ ɭɜɟɥɢɱɟɧɢɟ
Fibrinogen-like protein expressed in T lymphocytes
2- ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ
(pT49)
Ras guanine nucleotide ex10-ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ
change factor 2
Death associated transcrip4- ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ
tion factor 1
32
Microtubule-associated pro34-ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ
tein tau
Hypothetical protein
3- ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ
FLJ43213
Hypothetical protein
5- ɤɪɚɬɧɨɟ ɫɧɢɠɟɧɢɟ
FLJ31897
62
Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɩɪɨɞɟɦɨɧɫɬɪɢɪɨɜɚɧɨ, ɱɬɨ ɢɫɩɨɥɶɡɭɟɦɚɹ ɦɟɬɨɞɢɤɚ
ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ ɹɜɥɹɟɬɫɹ ɷɮɮɟɤɬɢɜɧɵɦ ɢɧɫɬɪɭɦɟɧɬɨɦ ɞɥɹ ɦɨɧɢɬɨɪɢɧɝɚ ɢɡɦɟɧɟɧɢɣ ɛɟɥɤɨɜ ɜɚɠɧɟɣɲɢɯ ɤɥɟɬɨɤ «ɧɢɲɢ» ȽɋɄ ɜ ɨɬɜɟɬ ɧɚ
ɝɨɪɦɨɧɚɥɶɧɭɸ ɫɬɢɦɭɥɹɰɢɸ.
3.2 Ⱥɧɚɥɢɡ ɩɪɨɬɟɨɦɚ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ
3.2.1 Ɇɨɧɨɧɭɤɥɟɚɪɧɵɟ ɤɥɟɬɤɢ
ɉɨɩɭɥɹɰɢɹ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɤɥɟɬɨɤ (ɆɇɄ) ɛɵɥɚ ɜɵɞɟɥɟɧɚ ɢɡ ɨɞɧɨɝɨ ɨɛɪɚɡɰɚ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ (ɉɄ). Ɋɚɡɞɟɥɟɧɢɟ ɟɝɨ ɧɚ ɞɜɟ ɱɚɫɬɢ
ɩɪɢɜɟɥɨ ɤ ɨɛɪɚɡɨɜɚɧɢɸ ɨɛɪɚɡɰɨɜ (Ⱥ ɢ Ȼ) ɩɨ ɨɞɧɨɦɭ ɦɢɥɥɢɨɧɭ ɆɇɄ,
ɤɨɬɨɪɵɟ ɡɚɬɟɦ ɛɵɥɢ ɩɨɞɜɟɪɝɧɭɬɵ ɩɪɨɬɟɨɦɧɨɦɭ ɚɧɚɥɢɡɭ ɤɚɤ ɨɩɢɫɚɧɨ ɜ
ɪɚɡɞɟɥɟ «Ɇɟɬɨɞɵ». Ⱦɜɟ ɚɥɢɤɜɨɬɵ Ⱥ ɢ Ȼ ɛɵɥɢ ɢɫɫɥɟɞɨɜɚɧɵ ɩɚɪɚɥɥɟɥɶɧɨ, ɱɬɨ ɩɪɢɜɟɥɨ ɤ ɩɨɥɭɱɟɧɢɸ ɜɡɚɢɦɨɫɜɹɡɚɧɧɵɯ ɩɪɨɬɟɨɦɧɵɯ ɩɪɨɮɢɥɟɣ
ɩɨɩɭɥɹɰɢɢ ɆɇɄ.
Ɋɚɡɞɟɥɟɧɢɟ ɜ ɝɟɥɟ ɜɫɟɯ ɱɟɬɵɪɟɯ ɮɪɚɤɰɢɣ, ɩɨɥɭɱɟɧɧɵɯ ɩɨɫɥɟ ɥɢɡɢɫɚ
ɜɧɟɲɧɟɣ ɦɟɦɛɪɚɧɵ ɆɇɄ (ɫɦ. ɪɚɡɞɟɥ «Ɇɟɬɨɞɵ») – Ⱥ ɢ Ȼ ɜ ɞɜɨɣɧɨɣ ɩɨɜɬɨɪɧɨɫɬɢ – ɩɨɤɚɡɚɧɨ ɧɚ ɢɡɨɛɪɚɠɟɧɢɹɯ ɝɟɥɟɣ ɧɢɠɟ (ɪɢɫ. 3.1–3.4).
Ⱥ
Ȼ
Ɋɢɫ. 3.1. ɉɪɨɬɟɨɦɧɵɟ ɩɪɨɮɢɥɢ ɩɪɢ ɪɚɡɞɟɥɟɧɢɢ ɜ ɝɟɥɟ ɩɟɪɜɨɣ ɮɪɚɤɰɢɢ
ɆɇɄ ɢɡ ɨɞɧɨɣ ɚɥɢɤɜɨɬɵ ɜ ɞɜɨɣɧɨɣ ɩɨɜɬɨɪɧɨɫɬɢ (Ⱥ ɢ Ȼ).
63
Ⱥ
Ȼ
Ɋɢɫ. 3.2. ɉɪɨɬɟɨɦɧɵɟ ɩɪɨɮɢɥɢ ɩɪɢ ɪɚɡɞɟɥɟɧɢɢ ɜ ɝɟɥɟ ɜɬɨɪɨɣ ɮɪɚɤɰɢɢ
ɆɇɄ ɢɡ ɨɞɧɨɣ ɚɥɢɤɜɨɬɵ ɜ ɞɜɨɣɧɨɣ ɩɨɜɬɨɪɧɨɫɬɢ (Ⱥ ɢ Ȼ).
Ⱥ
Ȼ
Ɋɢɫ. 3.3. ɉɪɨɬɟɨɦɧɵɟ ɩɪɨɮɢɥɢ ɩɪɢ ɪɚɡɞɟɥɟɧɢɢ ɜ ɝɟɥɟ ɬɪɟɬɶɟɣ ɮɪɚɤɰɢɢ
ɆɇɄ ɢɡ ɨɞɧɨɣ ɚɥɢɤɜɨɬɵ ɜ ɞɜɨɣɧɨɣ ɩɨɜɬɨɪɧɨɫɬɢ (Ⱥ ɢ Ȼ).
Ⱥ
Ȼ
Ɋɢɫ. 3.4. ɉɪɨɬɟɨɦɧɵɟ ɩɪɨɮɢɥɢ ɩɪɢ ɪɚɡɞɟɥɟɧɢɢ ɜ ɝɟɥɟ ɱɟɬɜɟɪɬɨɣ
ɮɪɚɤɰɢɢ ɆɇɄ ɢɡ ɨɞɧɨɣ ɚɥɢɤɜɨɬɵ ɜ ɞɜɨɣɧɨɣ ɩɨɜɬɨɪɧɨɫɬɢ (Ⱥ ɢ Ȼ).
64
ɉɪɟɞɫɬɚɜɥɟɧɧɵɟ ɜɵɲɟ ɢɡɨɛɪɚɠɟɧɢɹ ɯɚɪɚɤɬɟɪɢɡɭɸɬ ɩɪɨɬɟɨɦɧɵɣ
ɩɪɨɮɢɥɶ ɩɨɩɭɥɹɰɢɢ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɫɬɜɨɥɨɜɵɯ
ɤɥɟɬɨɤ (ɆɇɄ). Ɍɨɬ ɮɚɤɬ, ɱɬɨ ɤɥɟɬɤɢ ɛɵɥɢ ɜɵɞɟɥɟɧɵ ɢɡ ɨɞɧɨɝɨ ɨɛɪɚɡɰɚ, ɨɡɧɚɱɚɟɬ, ɱɬɨ ɩɨɩɭɥɹɰɢɹ ɤɥɟɬɨɤ ɫɨɨɬɜɟɬɫɬɜɭɟɬ ɨɞɧɨɦɭ ɢɧɞɢɜɢɞɭɭɦɭ (ɞɨɧɨɪɭ). Ɋɚɡɞɟɥɟɧɢɟ ɨɛɪɚɡɰɚ ɧɚ ɞɜɟ ɱɚɫɬɢ ɩɨɡɜɨɥɢɥɨ ɩɨɥɭɱɢɬɶ ɞɜɟ
ɩɨɪɰɢɢ ɩɨ 106 ɤɥɟɬɨɤ ɞɥɹ ɩɪɨɬɟɨɦɧɵɯ ɢɫɫɥɟɞɨɜɚɧɢɣ.
ɉɪɢ ɷɬɨɦ ɩɪɟɫɥɟɞɨɜɚɥɢɫɶ ɞɜɟ ɰɟɥɢ: 1) ɨɩɪɟɞɟɥɢɬɶ ɩɪɨɬɟɨɦɧɵɣ
ɩɪɨɮɢɥɶ ɆɇɄ; 2) ɭɫɬɚɧɨɜɢɬɶ ɜɨɡɦɨɠɧɭɸ ɜɚɪɢɚɛɟɥɶɧɨɫɬɶ ɞɚɧɧɵɯ ɩɨ
ɞɜɭɦ ɩɪɨɛɚɦ.
ɂɡɨɛɪɚɠɟɧɢɹ ɝɟɥɟɣ ɨɬɪɚɠɚɸɬ ɫɯɨɞɫɬɜɨ ɩɨɥɭɱɟɧɧɵɯ ɩɪɨɬɟɨɦɧɵɯ
ɩɪɨɮɢɥɟɣ ɢ ɭɤɚɡɵɜɚɸɬ ɧɚ ɬɨ, ɱɬɨ ɚɥɢɤɜɨɬɵ, ɢɫɫɥɟɞɭɟɦɵɟ ɩɚɪɚɥɥɟɥɶɧɨ
ɢ ɨɞɧɨɜɪɟɦɟɧɧɨ, ɩɪɢɜɨɞɹɬ ɤ ɩɨɥɭɱɟɧɢɸ ɩɪɚɤɬɢɱɟɫɤɢ ɨɞɢɧɚɤɨɜɵɯ ɪɟɡɭɥɶɬɚɬɨɜ.
Ⱦɥɹ ɭɝɥɭɛɥɟɧɧɨɣ ɨɰɟɧɤɢ ɪɚɡɥɢɱɢɣ ɦɟɠɞɭ ɨɞɢɧɚɤɨɜɵɦɢ ɨɛɪɚɡɰɚɦɢ, ɢɫɫɥɟɞɭɟɦɵɦɢ ɩɚɪɚɥɥɟɥɶɧɨ, ɢɡɨɛɪɚɠɟɧɢɹ ɛɵɥɢ ɩɨɞɜɟɪɝɧɭɬɵ ɞɨɩɨɥɧɢɬɟɥɶɧɨɦɭ ɚɧɚɥɢɡɭ ɫ ɩɨɦɨɳɶɸ ɫɩɟɰɢɚɥɶɧɨɝɨ ɩɚɤɟɬɚ ɩɪɨɝɪɚɦɦ
Phoretix Evolution (Nonlinear Dynamics) ɢ ɫɨɡɞɚɧɢɹ ɨɛɨɛɳɟɧɧɨɝɨ (ɦɨɧɬɚɠɧɨɝɨ) ɢɡɨɛɪɚɠɟɧɢɹ – ɛɟɥɤɨɜɨɣ ɤɚɪɬɵ.
ɗɬɨ ɛɵɥɨ ɫɞɟɥɚɧɨ ɞɥɹ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɢɡɦɟɧɟɧɢɣ, ɜɨɡɧɢɤɚɸɳɢɯ
ɬɨɥɶɤɨ ɜɫɥɟɞɫɬɜɢɟ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɯ ɭɫɥɨɜɢɣ, ɢ ɞɥɹ ɨɩɪɟɞɟɥɟɧɢɹ
ɨɠɢɞɚɟɦɨɣ ɜɚɪɢɚɰɢɢ ɞɚɧɧɵɯ, ɧɟ ɡɚɜɢɫɹɳɟɣ ɨɬ ɪɟɝɭɥɢɪɭɸɳɟɝɨ ɜɥɢɹɧɢɹ ɨɤɪɭɠɟɧɢɹ ɧɚ ɛɟɥɤɢ ɆɇɄ. Ɏɪɚɤɰɢɨɧɢɪɭɹ ɨɛɪɚɡɰɵ ɜ ɱɟɬɵɪɟ ɪɚɡɧɵɟ ɮɪɚɤɰɢɢ, ɦɨɠɧɨ ɛɵɥɨ ɢɡɭɱɢɬɶ ɤɚɠɞɭɸ ɮɪɚɤɰɢɸ ɛɨɥɟɟ ɬɳɚɬɟɥɶɧɨ
ɢ ɨɩɪɟɞɟɥɢɬɶ ɫ ɛɨɥɶɲɟɣ ɭɜɟɪɟɧɧɨɫɬɶɸ ɜɟɪɨɹɬɧɨɫɬɶ ɨɲɢɛɤɢ ɞɥɹ ɢɫɯɨɞɧɨɝɨ ɨɛɪɚɡɰɚ ɜ ɰɟɥɨɦ.
ɉɨɫɬɪɨɟɧɢɟ ɦɨɧɬɚɠɧɨɝɨ ɢɡɨɛɪɚɠɟɧɢɹ ɨɫɭɳɟɫɬɜɥɹɥɨɫɶ ɜ ɜɢɞɟ ɧɟɫɤɨɥɶɤɢɯ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɵɯ ɷɬɚɩɨɜ. ɋɧɚɱɚɥɚ ɜɵɩɨɥɧɹɥɫɹ ɩɪɨɝɪɚɦɦɧɵɣ ɚɧɚɥɢɡ ɢɡɨɛɪɚɠɟɧɢɣ ɫ ɰɟɥɶɸ ɚɜɬɨɦɚɬɢɱɟɫɤɨɝɨ ɜɵɹɜɥɟɧɢɹ ɨɤɪɚ65
ɲɟɧɧɵɯ ɩɹɬɟɧ ɢ ɭɫɬɚɧɨɜɥɟɧɢɹ ɢɯ ɨɱɟɪɬɚɧɢɣ. Ɉɤɪɚɲɟɧɧɚɹ ɩɥɨɳɚɞɶ
ɤɚɠɞɨɝɨ ɩɹɬɧɚ ɭɫɬɚɧɚɜɥɢɜɚɥɚɫɶ ɩɪɨɝɪɚɦɦɨɣ ɩɨ ɪɟɡɭɥɶɬɚɬɚɦ ɨɩɪɟɞɟɥɟɧɢɹ ɪɚɡɥɢɱɢɣ ɦɟɠɞɭ «ɬɟɦɧɵɦɢ» ɢ «ɫɜɟɬɥɵɦɢ» ɩɢɤɫɟɥɹɦɢ.
ɉɨɫɤɨɥɶɤɭ ɩɹɬɧɚ ɢɦɟɸɬ ɪɚɡɧɭɸ ɫɬɟɩɟɧɶ ɨɤɪɚɫɤɢ ɢ ɦɨɝɭɬ ɫɥɢɜɚɬɶɫɹ ɫ ɮɨɧɨɦ, ɜ ɩɪɨɝɪɚɦɦɟ ɡɚɞɚɸɬɫɹ ɬɪɢ ɫɩɟɰɢɚɥɶɧɵɯ ɩɚɪɚɦɟɬɪɚ
ɞɥɹ ɜɵɹɜɥɟɧɢɹ ɛɟɥɤɨɜɵɯ ɮɪɚɤɰɢɣ (ɩɹɬɟɧ, «spots»). Ɉɞɢɧ ɢɡ ɧɢɯ – ɩɚɪɚɦɟɬɪ «ɋɝɥɚɠɢɜɚɧɢɟ» («Smooth») ɫ ɩɨɦɨɳɶɸ ɚɥɝɨɪɢɬɦɚ ɞɢɮɮɭɡɧɨɝɨ ɫɝɥɚɠɢɜɚɧɢɹ ɨɛɟɫɩɟɱɢɜɚɟɬ ɢɞɟɧɬɢɮɢɤɚɰɢɸ ɧɚɢɛɨɥɟɟ ɫɢɥɶɧɨ ɜɵɪɚɠɟɧɧɵɯ ɩɹɬɟɧ, ɚ ɬɚɤɠɟ ɱɟɬɤɨɫɬɶ ɨɩɪɟɞɟɥɟɧɢɹ ɤɪɚɹ ɩɹɬɧɚ. Ⱦɥɹ ɬɨɝɨ,
ɱɬɨɛɵ ɨɬɞɟɥɢɬɶ ɫɥɚɛɨ ɨɤɪɚɲɟɧɧɵɟ ɩɹɬɧɚ ɨɬ ɮɨɧɚ ɢ ɲɭɦɚ, ɢɡɦɟɧɹɟɬɫɹ
ɩɚɪɚɦɟɬɪ «ȼɵɞɟɥɟɧɢɟ» («Saliency»). Ɍɪɟɬɢɣ ɩɚɪɚɦɟɬɪ «Ɇɢɧɢɦɚɥɶɧɚɹ
ɩɥɨɳɚɞɶ» («Min Area») ɡɚɞɚɟɬ ɦɢɧɢɦɚɥɶɧɭɸ ɩɥɨɳɚɞɶ ɩɹɬɧɚ ɢ ɜɫɟ
ɩɹɬɧɚ, ɨɛɥɚɞɚɸɳɢɟ ɩɥɨɳɚɞɶɸ ɧɢɠɟ ɷɬɨɝɨ ɡɧɚɱɟɧɢɹ, ɧɟ ɛɭɞɭɬ ɜɵɹɜɥɟɧɵ.
Ⱦɚɥɟɟ ɧɚ ɜɬɨɪɨɦ ɷɬɚɩɟ ɨɛɪɚɛɨɬɤɢ ɢɡɨɛɪɚɠɟɧɢɣ ɨɫɭɳɟɫɬɜɥɹɟɬɫɹ
ɫɛɨɪ ɫɜɟɞɟɧɢɣ ɨ ɩɹɬɧɚɯ ɢ ɩɨɫɬɪɨɟɧɢɟ ɬɪɟɯɦɟɪɧɵɯ ɦɨɞɟɥɟɣ ɧɚ ɢɯ ɨɫɧɨɜɟ. Ⱥɧɚɥɢɡ ɩɹɬɟɧ ɢɞɟɬ ɩɨ ɬɪɟɦ ɨɫɧɨɜɧɵɦ ɩɚɪɚɦɟɬɪɚɦ: «ɢɧɬɟɧɫɢɜɧɨɫɬɶ», «ɩɥɨɳɚɞɶ» ɢ «ɨɛɴɟɦ ɩɹɬɧɚ». «ɂɧɬɟɧɫɢɜɧɨɫɬɶ» – ɩɨɤɚɡɵɜɚɟɬ
ɫɬɟɩɟɧɶ ɨɤɪɚɲɢɜɚɧɢɹ ɩɹɬɧɚ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɮɨɧɨɦ; ɩɪɢ ɷɬɨɦ ɛɟɪɟɬɫɹ
ɡɧɚɱɟɧɢɟ ɧɚɢɛɨɥɟɟ ɫɢɥɶɧɨ ɨɤɪɚɲɟɧɧɵɯ ɩɢɤɫɟɥɟɣ ɫɚɦɨɝɨ ɩɹɬɧɚ ɢ
ɧɚɢɛɨɥɟɟ ɫɜɟɬɥɨɣ ɨɛɥɚɫɬɢ ɛɥɢɠɚɣɲɟɝɨ ɮɨɧɚ, ɨɤɪɭɠɚɸɳɟɝɨ ɩɹɬɧɨ.
«ɉɥɨɳɚɞɶ ɩɹɬɧɚ» – ɞɚɧɧɵɣ ɩɚɪɚɦɟɬɪ ɜɵɫɱɢɬɵɜɚɟɬ ɩɨ ɫɪɟɞɧɟɦɭ ɡɧɚɱɟɧɢɸ ɢɧɬɟɧɫɢɜɧɨɫɬɢ ɨɤɪɚɲɢɜɚɧɢɹ. «Ɉɛɴɟɦ ɩɹɬɧɚ» – ɜɵɱɢɫɥɹɟɬɫɹ ɢɡ
ɩɨɤɚɡɚɬɟɥɹ ɩɥɨɳɚɞɶ ɩɹɬɧɚ, ɪɚɫɫɱɢɬɵɜɚɟɦɨɝɨ ɫɬɪɨɝɨ ɩɨ ɥɢɧɢɢ ɨɛɜɨɞɤɢ ɩɹɬɧɚ.
ɂɬɨɝɨɜɵɟ ɬɪɟɯɦɟɪɧɵɟ ɦɨɞɟɥɢ ɩɪɟɞɫɬɚɜɥɹɸɬ ɫɨɛɨɣ ɧɚɛɨɪɵ ɩɢɤɨɜ;
ɩɪɢ ɷɬɨɦ, ɱɟɦ ɛɨɥɶɲɟ ɢɧɬɟɧɫɢɜɧɨɫɬɶ, ɬɟɦ ɜɵɲɟ ɩɢɤ, ɢ ɬɟɦ ɛɨɥɶɲɟ
ɤɨɧɰɟɧɬɪɚɰɢɹ ɛɟɥɤɚ ɜ ɞɚɧɧɨɣ ɮɪɚɤɰɢɢ.
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ȼɚɠɧɵɦ ɞɨɫɬɨɢɧɫɬɜɨɦ ɩɪɨɝɪɚɦɦɵ Phoretix Evolution ɹɜɥɹɟɬɫɹ ɬɨ,
ɱɬɨ ɨɧɚ ɩɨɡɜɨɥɹɟɬ ɩɪɨɜɨɞɢɬɶ ɫɪɚɜɧɢɬɟɥɶɧɵɣ ɚɧɚɥɢɡ ɧɟɫɤɨɥɶɤɢɯ ɢɡɨɛɪɚɠɟɧɢɣ ɞɜɭɦɟɪɧɵɯ ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦ (Ⱦɗ). ɉɪɢ ɪɟɲɟɧɢɢ ɩɨɞɨɛɧɵɯ ɡɚɞɚɱ ɨɛɳɢɟ ɩɹɬɧɚ, ɯɚɪɚɤɬɟɪɧɵɟ ɞɥɹ 2-ɯ ɢ ɛɨɥɟɟ Ⱦɗ, ɜɵɞɟɥɹɸɬɫɹ
ɨɞɧɢɦ ɰɜɟɬɨɦ. Ⱦɚɥɟɟ ɞɥɹ ɧɢɯ ɦɨɠɧɨ ɡɚɞɚɬɶ ɫɪɟɞɧɟɚɪɢɮɦɟɬɢɱɟɫɤɢɟ
ɯɚɪɚɤɬɟɪɢɫɬɢɤɢ, ɚ ɬɚɤɠɟ ɪɚɫɫɱɢɬɚɬɶ ɜɚɪɢɚɛɟɥɶɧɨɫɬɶ ɷɬɢɯ ɩɹɬɟɧ ɢ ɩɨɥɭɱɢɬɶ ɢɧɵɟ ɞɚɧɧɵɟ. ȿɫɥɢ ɩɪɢ ɚɧɚɥɢɡɟ ɫɪɚɜɧɢɜɚɟɦɵɯ ɢɡɨɛɪɚɠɟɧɢɣ
ɜɵɹɜɥɹɸɬɫɹ ɩɹɬɧɚ, ɩɪɢɫɭɬɫɬɜɭɸɳɢɟ ɧɚ ɨɞɧɨɦ ɢɡɨɛɪɚɠɟɧɢɢ ɢ ɨɬɫɭɬɫɬɜɭɸɳɢɟ ɧɚ ɞɪɭɝɨɦ, ɥɢɛɨ ɨɬɥɢɱɚɸɳɢɟɫɹ ɤɨɥɢɱɟɫɬɜɟɧɧɨ ɢ ɤɚɱɟɫɬɜɟɧɧɨ
ɜ ɡɧɚɱɢɬɟɥɶɧɨɣ ɫɬɟɩɟɧɢ, ɬɨ ɨɧɢ ɜɵɞɟɥɹɸɬɫɹ ɞɪɭɝɢɦ ɰɜɟɬɨɦ. Ɍɚɤɢɦ
ɨɛɪɚɡɨɦ, ɩɨɹɜɥɹɟɬɫɹ ɨɱɟɧɶ ɭɞɨɛɧɵɣ ɢɧɫɬɪɭɦɟɧɬ ɞɚɠɟ ɞɥɹ ɜɢɡɭɚɥɶɧɨɝɨ
ɚɧɚɥɢɡɚ Ⱦɗ, ɨɫɨɛɟɧɧɨ ɩɪɢ ɛɨɥɶɲɨɦ ɤɨɥɢɱɟɫɬɜɟ ɝɟɥɟɣ.
ȼ ɩɪɨɰɟɫɫɟ ɬɚɤɨɝɨ ɚɧɚɥɢɡɚ ɜɫɟɦ ɨɛɧɚɪɭɠɟɧɧɵɦ ɩɹɬɧɚɦ ɚɜɬɨɦɚɬɢɱɟɫɤɢ ɩɪɢɫɜɚɢɜɚɟɬɫɹ ɭɧɢɤɚɥɶɧɵɣ ɧɨɦɟɪ, ɚ ɬɚɤɠɟ ɪɚɫɫɱɢɬɵɜɚɸɬɫɹ
ɜɟɥɢɱɢɧɵ ɢɧɬɟɧɫɢɜɧɨɫɬɢ ɩɥɨɳɚɞɢ, ɨɛɴɟɦɚ ɢ ɢɯ ɩɪɨɰɟɧɬɧɵɯ ɫɨɨɬɧɨɲɟɧɢɣ. ȼɫɟ ɷɬɢ ɯɚɪɚɤɬɟɪɢɫɬɢɤɢ ɨɬɨɛɪɚɠɚɸɬɫɹ ɜ ɜɢɞɟ ɨɬɱɟɬɚ, ɤɨɬɨɪɵɣ ɡɚɬɟɦ ɦɨɠɧɨ ɷɤɫɩɨɪɬɢɪɨɜɚɬɶ ɜ ɪɚɡɥɢɱɧɵɟ ɩɪɢɥɨɠɟɧɢɹ. ɉɨɫɤɨɥɶɤɭ ɢɫɫɥɟɞɨɜɚɬɟɥɟɣ ɨɛɵɱɧɨ ɢɧɬɟɪɟɫɭɟɬ ɨɛɴɟɦ ɩɹɬɧɚ, ɤɨɬɨɪɵɣ ɜɵɱɢɫɥɹɟɬɫɹ ɫɬɪɨɝɨ ɩɨ ɥɢɧɢɢ ɨɛɜɨɞɤɢ ɩɹɬɧɚ, ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɟ ɞɚɧɧɵɟ ɞɥɹ
ɫɪɚɜɧɟɧɢɹ ɩɹɬɟɧ ɦɨɝɭɬ ɛɵɬɶ ɩɨɥɭɱɟɧɵ ɢɡ ɤɨɥɨɧɤɢ «Volume». Ⱦɥɹ ɬɨɝɨ, ɱɬɨɛɵ ɬɨɱɧɨ ɨɩɪɟɞɟɥɢɬɶ ɫɨɨɬɜɟɬɫɬɜɢɟ ɯɚɪɚɤɬɟɪɢɫɬɢɤ ɜ ɤɨɦɩɶɸɬɟɪɧɨɦ ɨɬɱɟɬɟ ɨɩɪɟɞɟɥɟɧɧɨɦɭ ɩɹɬɧɭ ɧɚ ɤɚɪɬɟ, ɜ ɩɪɨɝɪɚɦɦɟ ɡɚɩɭɫɤɚɟɬɫɹ ɮɭɧɤɰɢɹ ɨɬɨɛɪɚɠɟɧɢɹ ɧɨɦɟɪɚ ɩɹɬɧɚ ɧɚ ɫɚɦɨɣ ɤɚɪɬɟ, ɚ ɡɚɬɟɦ ɨɧ
ɫɪɚɜɧɢɜɚɟɬɫɹ ɫ ɧɨɦɟɪɨɦ («SpotID») ɜ ɨɬɱɟɬɟ.
Ⱦɥɹ ɭɥɭɱɲɟɧɢɹ ɬɨɱɧɨɫɬɢ ɫɪɚɜɧɟɧɢɹ ɝɟɥɟɣ ɜ ɩɪɨɝɪɚɦɦɟ ɢɦɟɟɬɫɹ
ɮɭɧɤɰɢɹ ɜɵɫɬɚɜɥɟɧɢɹ ɨɩɨɪɧɵɯ ɬɨɱɟɤ, ɛɥɚɝɨɞɚɪɹ ɤɨɬɨɪɨɣ ɜ ɤɚɠɞɨɦ
ɝɟɥɟ ɦɨɠɧɨ ɜɵɫɬɚɜɢɬɶ ɨɩɨɪɧɵɟ (ɪɟɮɟɪɟɧɫɧɵɟ) ɬɨɱɤɢ ɧɚ ɩɹɬɧɚɯ, ɤɨɬɨɪɵɟ ɩɪɢɫɭɬɫɬɜɭɸɬ ɧɚ ɨɛɟɢɯ ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦɚɯ. Ɉɩɨɪɧɵɟ ɬɨɱɤɢ
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ɜɤɥɸɱɚɸɬɫɹ ɜ ɚɧɚɥɢɡ ɢ ɬɨɱɧɨɫɬɶ ɜɨɡɪɚɫɬɚɟɬ. Ʉɨɧɟɱɧɵɦ ɪɟɡɭɥɶɬɚɬɨɦ
ɹɜɥɹɟɬɫɹ ɬɪɟɯɦɟɪɧɚɹ ɦɨɞɟɥɶ ɩɹɬɧɚ, ɩɪɟɞɫɬɚɜɥɟɧɧɚɹ ɜ ɜɢɞɟ ɩɢɤɚ, ɤɨɬɨɪɵɣ ɨɬɨɛɪɚɠɚɟɬ ɮɨɪɦɭ ɢ ɨɛɴɟɦ ɩɹɬɧɚ.
Ɋɚɛɨɬɚɹ ɫ ɤɨɥɥɟɤɰɢɟɣ ɞɜɭɦɟɪɧɵɯ ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦ, ɦɨɠɧɨ ɨɩɢɫɚɧɧɵɦ ɫɩɨɫɨɛɨɦ ɩɨɫɬɪɨɢɬɶ ɨɛɨɛɳɟɧɧɨɟ, ɫɬɚɧɞɚɪɬɢɡɢɪɨɜɚɧɧɨɟ ɦɨɧɬɚɠɧɨɟ ɢɡɨɛɪɚɠɟɧɢɟ – ɫɨɨɬɜɟɬɫɬɜɭɸɳɭɸ ɛɟɥɤɨɜɭɸ ɤɚɪɬɭ.
Ʉɚɤ ɫɥɟɞɭɟɬ ɢɡ ɩɨɥɭɱɟɧɧɵɯ ɪɟɡɭɥɶɬɚɬɨɜ (ɪɢɫ. 3.1–3.4), ɜɨɫɩɪɨɢɡɜɨɞɢɦɨɫɬɶ ɪɟɡɭɥɶɬɚɬɨɜ ɧɚɯɨɞɢɬɫɹ ɧɚ ɜɵɫɨɤɨɦ ɭɪɨɜɧɟ ɢ ɪɚɡɥɢɱɢɹ
ɬɪɭɞɧɨ ɨɛɧɚɪɭɠɢɬɶ ɛɟɡ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɤɨɦɩɶɸɬɟɪɧɨɝɨ ɚɧɚɥɢɡɚ. ɉɪɨɝɪɚɦɦɧɨɟ ɨɛɟɫɩɟɱɟɧɢɟ Phoretix (Nonlinear Dynamics) ɭɜɟɥɢɱɢɜɚɟɬ ɫɩɨɫɨɛɧɨɫɬɶ ɢɡɭɱɟɧɢɹ ɢɡɨɛɪɚɠɟɧɢɣ ɝɟɥɟɣ. Ʉɚɠɞɵɣ ɝɟɥɶ ɩɨɞɜɟɪɝɚɟɬɫɹ
ɫɤɚɧɢɪɨɜɚɧɢɸ ɫ ɩɨɥɭɱɟɧɢɟɦ 16-ɛɢɬ ɢɡɨɛɪɚɠɟɧɢɣ, ɱɬɨ ɨɛɟɫɩɟɱɢɜɚɟɬ
ɧɚɥɢɱɢɟ ɞɟɬɚɥɢɡɢɪɨɜɚɧɧɨɣ ɢɧɮɨɪɦɚɰɢɢ ɨ ɤɚɠɞɨɦ ɛɟɥɤɨɜɨɦ ɩɹɬɧɟ.
Ⱥɧɚɥɢɡɢɪɭɹ ɟɟ, ɤɨɦɩɶɸɬɟɪ ɜɵɞɟɥɹɟɬ ɛɟɥɤɨɜɵɟ ɩɹɬɧɚ ɤɚɠɞɨɝɨ ɝɟɥɹ ɢ
ɮɨɪɦɢɪɭɟɬ ɨɛɳɭɸ ɤɚɪɬɢɧɭ ɩɪɨɬɟɨɦɚ.
ɇɚɛɨɪ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɮɨɪɦɢɪɭɟɬ ɬ.ɧ. ɛɟɥɤɨɜɵɣ ɩɪɨɮɢɥɶ. Ʉɚɠɞɵɣ
ɢɧɞɢɜɢɞɭɚɥɶɧɵɣ ɨɛɪɚɡɟɰ ɜ ɧɚɲɟɦ ɫɥɭɱɚɟ ɞɚɟɬ ɧɟɫɤɨɥɶɤɨ ɨɬɥɢɱɧɵɣ ɧɚɛɨɪ, ɨɩɪɟɞɟɥɹɟɦɵɣ ɤɥɟɬɨɱɧɵɦɢ ɨɫɨɛɟɧɧɨɫɬɹɦɢ ɢɡɭɱɚɟɦɨɝɨ ɨɛɪɚɡɰɚ.
ɋɥɟɞɭɸɳɚɹ ɫɨɜɨɤɭɩɧɨɫɬɶ ɪɟɡɭɥɶɬɚɬɨɜ (ɪɢɫ. 3.5–3.10) ɩɪɟɞɫɬɚɜɥɹɟɬ
ɫɨɛɨɣ ɧɟ ɱɬɨ ɢɧɨɟ, ɤɚɤ ɢɥɥɸɫɬɪɚɰɢɸ ɦɟɬɨɞɢɱɟɫɤɨɝɨ ɩɨɞɯɨɞɚ, ɩɪɢɝɨɞɧɨɝɨ ɜ ɩɟɪɫɩɟɤɬɢɜɟ ɞɥɹ ɫɪɚɜɧɟɧɢɹ ɞɜɭɯ ɧɚɛɨɪɨɜ ɛɢɨɥɨɝɢɱɟɫɤɢ ɨɬɥɢɱɚɸɳɢɯɫɹ ɨɛɪɚɡɰɨɜ.
ɇɚ ɪɢɫ. 3.5–3.6 ɩɪɟɞɫɬɚɜɥɟɧɵ ɪɟɡɭɥɶɬɚɬɵ ɚɧɚɥɢɡɚ ɞɜɭɯ ɩɟɪɜɵɯ
ɮɪɚɤɰɢɣ ɞɜɭɯ ɚɥɢɤɜɨɬ. ɇɟɫɦɨɬɪɹ ɧɚ ɬɨ, ɱɬɨ ɞɜɚ ɨɛɪɚɡɰɚ ɩɪɨɢɫɯɨɞɹɬ
ɢɡ ɨɞɧɨɣ ɢ ɬɨɣ ɠɟ ɩɪɨɛɵ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ, ɞɜɚ ɪɟɡɭɥɶɬɢɪɭɸɳɢɯ
ɢɡɨɛɪɚɠɟɧɢɹ ɨɛɧɚɪɭɠɢɜɚɸɬ ɨɩɪɟɞɟɥɟɧɧɵɟ ɨɬɥɢɱɢɹ. Ɉɧɢ ɛɵɥɢ ɩɨɞɜɟɪɝɧɭɬɵ ɤɨɦɩɶɸɬɟɪɧɨɦɭ ɚɧɚɥɢɡɭ, ɚ ɛɟɥɤɨɜɵɟ ɩɪɨɮɢɥɢ ɤɚɠɞɨɝɨ ɨɛɪɚɡɰɚ (Ⱥ ɢ Ȼ) ɫɪɚɜɧɢɜɚɥɢɫɶ ɦɟɬɨɞɨɦ ɧɚɥɨɠɟɧɢɹ ɞɪɭɝ ɧɚ ɞɪɭɝɚ.
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ɇɚɥɨɠɟɧɢɟ ɢɡɨɛɪɚɠɟɧɢɣ Ⱥ ɢ Ȼ
ɞɥɹ ɩɟɪɜɨɣ ɮɪɚɤɰɢɢ
Ⱥ
Ȼ
ɐɜɟɬɨɜɵɟ ɨɬɥɢɱɢɹ ɩɪɢ ɫɪɚɜɧɟɧɢɢ ɨɞɢɧɚɤɨɜɵɯ ɩɹɬɟɧ
Ⱥ
Ȼ
4-ɤɪɚɬɧɨɟ ɭɜɟɥɢɱɟɧɢɟ ɨɛɴɟɦɚ
ɩɹɬɟɧ
Ɋɢɫ. 3.5. ɉɟɪɜɚɹ ɮɪɚɤɰɢɹ ɆɇɄ – ɭɝɥɭɛɥɟɧɧɨɟ ɢɡɭɱɟɧɢɟ ɩɪɨɬɟɨɦɧɨɝɨ
ɩɪɨɮɢɥɹ ɩɨɩɭɥɹɰɢɢ ɆɇɄ. Ⱦɜɚ ɨɛɪɚɡɰɚ ɩɨ 106 ɤɥɟɬɨɤ ɢɫɫɥɟɞɭɸɬɫɹ ɩɚɪɚɥɥɟɥɶɧɨ ɢ ɚɧɚɥɢɡɢɪɭɸɬɫɹ ɫ ɩɨɦɨɳɶɸ Phoretix software (Nonliner
Dynamics).
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Ɋɟɡɭɥɶɬɢɪɭɸɳɟɟ ɢɡɨɛɪɚɠɟɧɢɟ ɞɚɟɬ ɩɪɟɞɫɬɚɜɥɟɧɢɟ ɨ ɡɨɧɚɯ ɪɚɡɥɢɱɢɣ ɢ ɨɞɧɨɜɪɟɦɟɧɧɨ ɡɨɧɚɯ ɩɨɥɧɨɝɨ ɫɨɜɩɚɞɟɧɢɹ (ɡɟɥɟɧɵɣ ɰɜɟɬ ɧɚɞ ɪɨɡɨɜɵɦ, ɨɛɪɚɡɟɰ Ⱥ ɧɚɞ Ȼ). Ɋɚɡɧɵɟ ɩɹɬɧɚ ɨɛɜɟɞɟɧɵ ɢ ɫɨɩɨɫɬɚɜɥɟɧɵ ɞɥɹ
ɞɜɭɯ ɚɥɢɤɜɨɬ. ȼ ɷɬɨɦ ɫɥɭɱɚɟ ɨɛɪɚɡɟɰ Ⱥ ɢɫɩɨɥɶɡɨɜɚɧ ɤɚɤ ɪɟɮɟɪɟɧɫɧɵɣ
(ɷɬɚɥɨɧɧɵɣ). ɗɬɚɥɨɧ ɨɩɪɟɞɟɥɟɧ ɩɪɨɝɪɚɦɦɨɣ ɤɚɤ ɝɟɥɶ, ɢɦɟɸɳɢɣ ɧɚɢɛɨɥɶɲɟɟ ɤɨɥɢɱɟɫɬɜɨ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ. ɇɟɫɨɜɩɚɞɚɸɳɢɟ ɩɹɬɧɚ ɨɛɜɟɞɟɧɵ
ɫɟɪɨɣ ɥɢɧɢɟɣ, ɚ ɬɚɦ, ɝɞɟ ɩɹɬɧɚ ɨɛɜɟɞɟɧɵ ɰɜɟɬɚ ɦɨɪɫɤɨɣ ɜɨɥɧɵ ɥɢɧɢɟɣ –
ɧɚɛɥɸɞɚɟɬɫɹ ɫɨɜɩɚɞɟɧɢɟ ɞɥɹ ɨɛɨɢɯ ɨɛɪɚɡɰɨɜ.
ɉɹɬɧɚ, ɨɛɜɟɞɟɧɧɵɟ ɫɢɧɢɦ, ɹɜɥɹɸɬɫɹ ɩɹɬɧɚɦɢ ɨɛɪɚɡɰɚ Ⱥ, ɤɨɬɨɪɵɟ
ɜ ɞɜɚ ɪɚɡɚ ɛɨɥɶɲɟ ɜ ɨɛɴɟɦɟ, ɱɟɦ ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɟ ɩɹɬɧɚ ɜ ɨɛɪɚɡɰɟ Ȼ.
ɉɹɬɧɚ, ɨɛɜɟɞɟɧɧɵɟ ɤɪɚɫɧɵɦ, ɜ ɞɜɚ ɪɚɡɚ ɦɟɧɶɲɟ ɩɨ ɨɛɴɟɦɭ ɜ ɨɛɪɚɡɰɟ Ⱥ
ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɫɨɨɬɜɟɬɫɬɜɭɸɳɢɦɢ ɩɹɬɧɚɦɢ ɨɛɪɚɡɰɚ Ȼ. Ⱥɛɫɨɥɸɬɧɨɟ
ɱɢɫɥɨ ɩɹɬɟɧ (ɩɪɟɜɵɲɟɧɢɹ ɢɥɢ ɧɟɞɨɫɬɚɱɚ) ɧɟ ɢɦɟɟɬ ɛɨɥɶɲɨɝɨ ɡɧɚɱɟɧɢɹ, ɨɞɧɚɤɨ ɢɧɬɟɪɟɫɟɧ ɮɚɤɬɨɪ, ɫɩɨɫɨɛɫɬɜɭɸɳɢɣ ɷɬɨɦɭ. Ʉɚɤ ɛɵɥɨ ɨɩɪɟɞɟɥɟɧɨ ɜ ɚɧɚɥɢɬɢɱɟɫɤɨɦ ɷɤɫɩɟɪɢɦɟɧɬɟ (ɪɢɫ. 3.5), ɥɸɛɨɟ ɞɜɭɤɪɚɬɧɨɟ
ɩɪɟɜɵɲɟɧɢɟ ɜɟɥɢɱɢɧɵ ɩɹɬɧɚ ɹɜɥɹɟɬɫɹ ɡɧɚɱɢɦɵɦ. Ɏɚɤɬɢɱɟɫɤɢ, ɷɬɨ
ɤɪɢɬɟɪɢɣ, ɢɫɩɨɥɶɡɭɟɦɵɣ ɞɥɹ ɨɛɧɚɪɭɠɟɧɢɹ ɩɪɟɞɟɥɨɜ ɡɧɚɱɢɦɨɫɬɢ (ɛɨɥɟɟ ɩɨɞɪɨɛɧɨ ɨɛɫɭɠɞɟɧɨ ɧɢɠɟ). ȼɟɥɢɱɢɧɚ ɩɹɬɧɚ, ɩɨ ɫɭɬɢ, ɨɬɪɚɠɚɟɬ
ɨɛɳɟɟ ɤɨɥɢɱɟɫɬɜɨ ɩɪɢɫɭɬɫɬɜɭɸɳɟɝɨ ɛɟɥɤɚ.
ɉɪɢ ɚɧɚɥɢɡɟ ɆɇɄ ɢɡ ɨɞɧɨɝɨ ɨɛɪɚɡɰɚ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ ɦɵ ɩɨɩɵɬɚɥɢɫɶ ɭɫɬɚɧɨɜɢɬɶ ɩɨɪɨɝ ɡɧɚɱɢɦɨɫɬɢ (ɞɨɫɬɨɜɟɪɧɨɫɬɶ ɪɚɡɥɢɱɢɣ) ɢ
ɨɩɪɟɞɟɥɢɬɶ ɪɚɫɯɨɠɞɟɧɢɹ, ɜɵɡɜɚɧɧɵɟ ɢɫɤɥɸɱɢɬɟɥɶɧɨ ɯɨɞɨɦ ɷɤɫɩɟɪɢɦɟɧɬɚ. Ɋɚɡɞɟɥɟɧɢɟ, ɚ ɡɚɬɟɦ ɢɫɫɥɟɞɨɜɚɧɢɟ ɷɬɢɯ ɨɛɪɚɡɰɨɜ ɩɨ ɨɬɞɟɥɶɧɨɫɬɢ ɞɚɟɬ ɜɨɡɦɨɠɧɨɫɬɶ ɭɫɬɚɧɨɜɢɬɶ ɬɨɱɤɭ ɨɬɫɱɟɬɚ ɞɥɹ ɛɭɞɭɳɢɯ ɷɤɫɩɟɪɢɦɟɧɬɨɜ ɫ ɛɢɨɥɨɝɢɱɟɫɤɢ ɪɚɡɥɢɱɧɵɦɢ ɨɛɪɚɡɰɚɦɢ. ɉɨɪɨɝɨɜɨɟ ɡɧɚɱɟɧɢɟ
ɢɥɢ ɬ.ɧ. ɩɪɟɞɟɥ ɡɧɚɱɢɦɨɫɬɢ ɨɩɪɟɞɟɥɟɧ ɤɚɤ ɜɟɪɯɧɢɣ ɢ ɧɢɠɧɢɣ ɥɢɦɢɬ
ɡɧɚɱɢɦɨɫɬɢ ɢɡɦɟɧɟɧɢɹ ɜɟɥɢɱɢɧɵ ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ.
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ɇɚɥɨɠɟɧɢɟ ɢɡɨɛɪɚɠɟɧɢɣ Ⱥ ɢ Ȼ
ɞɥɹ ɜɬɨɪɨɣ ɮɪɚɤɰɢɢ
Ⱥ
Ȼ
ɐɜɟɬɨɜɵɟ ɨɬɥɢɱɢɹ ɩɪɢ ɫɪɚɜɧɟɧɢɢ ɨɞɢɧɚɤɨɜɵɯ ɩɹɬɟɧ
Ⱥ
Ȼ
Ⱥ
3-ɤɪɚɬɧɨɟ ɭɜɟɥɢɱɟɧɢɟ ɨɛɴɟɦɚ ɩɹɬɟɧ
Ⱥ
Ȼ
1.7-ɤɪɚɬɧɨɟ ɭɦɟɧɶɲɟɧɢɟ
ɨɛɴɟɦɚ ɩɹɬɟɧ
Ȼ
7-ɤɪɚɬɧɨɟ ɭɜɟɥɢɱɟɧɢɟ ɨɛɴɟɦɚ ɩɹɬɟɧ
Ɋɢɫ. 3.6. ȼɬɨɪɚɹ ɮɪɚɤɰɢɹ ɦɨɧɨɧɭɤɥɟɚɪɨɜ – ɭɝɥɭɛɥɟɧɧɨɟ ɢɡɭɱɟɧɢɟ ɩɪɨɬɟɨɦɧɵɯ ɩɪɨɮɢɥɟɣ.
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Ɂɧɚɱɢɦɵɟ ɢɡɦɟɧɟɧɢɹ – ɬɟ, ɤɨɬɨɪɵɟ ɩɨɹɜɥɹɸɬɫɹ ɜ ɪɟɡɭɥɶɬɚɬɟ ɤɚɤ
ɪɟɡɭɥɶɬɚɬ ɛɢɨɥɨɝɢɱɟɫɤɢɯ ɹɜɥɟɧɢɣ, ɚ ɧɟ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɯ ɩɪɨɰɟɞɭɪ.
ȼ ɫɜɨɸ ɨɱɟɪɟɞɶ, ɩɨɪɨɝɨɜɨɟ ɡɧɚɱɟɧɢɟ ɨɩɪɟɞɟɥɹɟɬɫɹ ɤɚɤ ɤɪɚɬɧɨɫɬɶ ɭɜɟɥɢɱɟɧɢɹ ɢɥɢ ɭɦɟɧɶɲɟɧɢɹ ɜɟɥɢɱɢɧɵ ɩɹɬɧɚ, ɨɬɪɚɠɚɸɳɟɝɨ ɨɛɴɟɦ ɞɚɧɧɨɝɨ ɛɟɥɤɚ.
Ⱦɥɹ ɨɩɪɟɞɟɥɟɧɢɹ ɩɪɟɞɟɥɨɜ ɡɧɚɱɢɦɨɫɬɢ, ɜɟɪɯɧɢɣ ɢ ɧɢɠɧɢɣ ɩɪɟɞɟɥɵ ɞɥɹ ɨɛɪɚɡɰɨɜ Ⱥ ɢ Ȼ ɢɡ ɨɞɧɨɣ ɩɪɨɛɵ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ ɛɵɥɢ
ɭɫɬɚɧɨɜɥɟɧɵ (ɪɢɫ. 3.7–3.10). Ⱥɧɚɥɢɡ 1-ɯ ɮɪɚɤɰɢɣ ɜɵɹɜɢɥ, ɱɬɨ ɜɟɪɯɧɢɣ ɩɪɟɞɟɥ ɭɜɟɥɢɱɟɧɢɹ ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ ɨɬ ɨɛɪɚɡɰɚ Ⱥ ɤ ɨɛɪɚɡɰɭ Ȼ
ɹɜɥɹɟɬɫɹ 11-ɤɪɚɬɧɵɦ (ɪɢɫ. 3.7). ɇɢɠɧɢɣ ɩɪɟɞɟɥ ɭɦɟɧɶɲɟɧɢɹ ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ ɹɜɥɹɟɬɫɹ 4-ɤɪɚɬɧɵɦ (ɪɢɫ. 3.8).
Ⱦɥɹ ɦɟɦɛɪɚɧɧɨɣ ɮɪɚɤɰɢɢ ɜɟɪɯɧɢɣ ɩɪɟɞɟɥ ɭɜɟɥɢɱɟɧɢɹ ɨɛɪɚɡɰɚ Ȼ
ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ Ⱥ ɹɜɥɹɟɬɫɹ 7-ɤɪɚɬɧɵɦ (ɪɢɫ. 3.9). ɇɢɠɧɢɣ ɩɪɟɞɟɥ (ɞɥɹ
ɦɟɦɛɪɚɧɧɵɯ ɮɪɚɤɰɢɣ) ɫɧɢɠɟɧɢɹ ɜɟɥɢɱɢɧɵ ɩɹɬɧɚ ɹɜɥɹɟɬɫɹ 4-ɤɪɚɬɧɵɦ
(ɪɢɫ. 3.10).
Ⱥ
Ȼ
Ⱥ
Ȼ
Ɋɢɫ. 3.7. ɉɟɪɜɚɹ ɮɪɚɤɰɢɹ ɦɨɧɨɧɭɤɥɟɚɪɨɜ – ɜɟɪɯɧɢɣ ɩɪɟɞɟɥ ɡɧɚɱɢɦɨɫɬɢ ɩɪɢ 11-ɤɪɚɬɧɨɦ ɭɜɟɥɢɱɟɧɢɢ ɪɚɡɦɟɪɚ ɩɹɬɧɚ.
72
Ⱥ
Ȼ
Ⱥ
Ȼ
Ɋɢɫ. 3.8. ɉɟɪɜɚɹ ɮɪɚɤɰɢɹ ɆɇɄ – ɧɢɠɧɢɣ ɩɪɟɞɟɥ ɡɧɚɱɢɦɨɫɬɢ ɩɪɢ 4ɤɪɚɬɧɨɦ ɭɦɟɧɶɲɟɧɢɢ ɪɚɡɦɟɪɚ ɩɹɬɧɚ
Ⱥ
Ȼ
Ⱥ
Ȼ
Ɋɢɫ. 3.9. ȼɬɨɪɚɹ ɮɪɚɤɰɢɹ ɆɇɄ – ɜɟɪɯɧɢɣ ɩɪɟɞɟɥ ɡɧɚɱɢɦɨɫɬɢ ɩɪɢ 11ɤɪɚɬɧɨɦ ɭɜɟɥɢɱɟɧɢɢ ɪɚɡɦɟɪɚ ɩɹɬɧɚ
73
Ⱥ
Ȼ
Ⱥ
Ȼ
Ɋɢɫ. 3.10. ȼɬɨɪɚɹ ɮɪɚɤɰɢɹ ɆɇɄ – ɧɢɠɧɢɣ ɩɪɟɞɟɥ ɡɧɚɱɢɦɨɫɬɢ ɩɪɢ 4ɤɪɚɬɧɨɦ ɭɦɟɧɶɲɟɧɢɢ ɪɚɡɦɟɪɚ ɩɹɬɧɚ
Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɦɵ ɩɨɥɚɝɚɟɦ, ɱɬɨ ɞɥɹ ɞɚɥɶɧɟɣɲɢɯ ɚɧɚɥɢɡɨɜ ɩɨɪɨɝɨɜɵɟ ɜɟɥɢɱɢɧɵ ɩɪɟɞɟɥɨɜ ɡɧɚɱɢɦɨɫɬɢ ɞɥɹ ɛɟɥɤɨɜɵɯ ɢɡɦɟɧɟɧɢɣ, ɮɢɤɫɢɪɭɟɦɵɯ ɩɨ ɜɟɥɢɱɢɧɟ ɩɹɬɧɚ, ɫɥɟɞɭɟɬ ɭɫɬɚɧɚɜɥɢɜɚɬɶ ɚɧɚɥɨɝɢɱɧɵɦ ɨɛɪɚɡɨɦ.
3.2.2 ɉɨɩɭɥɹɰɢɹ CD34+ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ
ɉɟɪɜɵɟ ɩɨɩɵɬɤɢ ɨɯɚɪɚɤɬɟɪɢɡɨɜɚɬɶ CD34+ȽɋɄ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ
ɦɟɬɨɞɨɜ ɩɪɨɬɟɨɦɢɤɢ ɛɵɥɢ ɨɝɪɚɧɢɱɟɧɵ ɧɢɡɤɢɦ ɫɨɞɟɪɠɚɧɢɟɦ ɛɟɥɤɚ
(106 ɤɥɟɬɨɤ). ɉɨɥɭɱɟɧɧɵɟ ɪɟɡɭɥɶɬɚɬɵ ɢɥɥɸɫɬɪɢɪɭɸɬɫɹ ɧɢɠɟ (ɪɢɫ.
3.11).
ȼɵɞɟɥɟɧɢɟ CD34+ȽɋɄ ɢɡ ɨɛɪɚɡɰɚ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ – ɫɥɨɠɧɚɹ
ɩɪɨɰɟɞɭɪɚ. ȼɵɯɨɞ ɱɚɫɬɨ ɹɜɥɹɟɬɫɹ ɧɢɡɤɢɦ ɢ ɞɚɟɬ ɧɟɞɨɫɬɚɬɨɱɧɨɟ ɤɨɥɢɱɟɫɬɜɨ ɤɥɟɬɨɤ. ɗɬɨ ɦɚɥɨɟ ɤɨɥɢɱɟɫɬɜɨ ɤɥɟɬɨɤ ɩɪɢɜɨɞɢɬ ɤ ɧɢɡɤɨɣ ɱɭɜɫɬ-
74
ɜɢɬɟɥɶɧɨɫɬɢ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ. ɉɪɨɜɟɞɟɧɧɵɟ ɧɚ ɤɥɟɬɤɚɯ ɨɫɬɟɨɫɚɪɤɨɦɵ ɷɤɫɩɟɪɢɦɟɧɬɵ ɩɨɤɚɡɚɥɢ, ɱɬɨ ɜɟɪɯɧɢɟ ɩɪɟɞɟɥɵ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ
ɞɨɫɬɢɝɚɸɬɫɹ ɩɪɢ ɚɧɚɥɢɡɟ ɨɛɪɚɡɰɚ, ɫɨɞɟɪɠɚɳɟɝɨ 3×106 ɤɥɟɬɨɤ. Ⱦɚɥɶɧɟɣɲɢɟ ɢɫɫɥɟɞɨɜɚɧɢɹ ɧɚ ɆɇɄ ɭɫɬɚɧɨɜɢɥɢ, ɱɬɨ ɤɨɥɢɱɟɫɬɜɨ 1×106 ɤɥɟɬɨɤ ɹɜɥɹɸɬɫɹ ɢɞɟɚɥɶɧɵɦ ɧɚɛɨɪɨɦ ɞɥɹ ɞɢɧɚɦɢɱɟɫɤɨɝɨ ɩɪɨɦɟɠɭɬɤɚ.
ɗɬɢ ɨɛɫɬɨɹɬɟɥɶɫɬɜɚ ɛɵɥɢ ɭɱɬɟɧɵ ɩɪɢ ɢɫɫɥɟɞɨɜɚɧɢɢ CD34+ ɤɥɟɬɨɤ.
Ɍɟɦ ɧɟ ɦɟɧɟɟ, ɩɨɥɭɱɟɧɧɵɟ 2 ɝɟɥɹ ɞɥɹ CD34+ ɤɥɟɬɨɤ ɭɤɚɡɵɜɚɸɬ ɧɚ
ɬɨ, ɱɬɨ ɤɨɥɢɱɟɫɬɜɨ 1×106 ɤɥɟɬɨɤ ɹɜɥɹɟɬɫɹ ɧɟɞɨɫɬɚɬɨɱɧɵɦ. Ⱦɜɚ ɨɛɪɚɡɰɚ
(Ⱥ ɢ Ȼ), ɜɵɞɟɥɟɧɧɵɟ ɢɡ ɞɜɭɯ ɪɚɡɧɵɯ ɩɪɨɛ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ, ɛɵɥɢ
ɩɪɨɚɧɚɥɢɡɢɪɨɜɚɧɵ (ɪɢɫ. 3.11). Ɉɛɪɚɡɟɰ Ⱥ ɫɨɞɟɪɠɚɥ 1×106 CD34+ ɤɥɟɬɨɤ, ɚ ɨɛɪɚɡɟɰ ȼ – 1,4×106 CD34+ ɤɥɟɬɨɤ. ɉɪɟɞɫɬɚɜɥɹɟɬɫɹ, ɱɬɨ 1-ɹ
ɮɪɚɤɰɢɹ ɨɛɪɚɡɰɚ Ȼ ɢɦɟɥɚ ɧɟɫɤɨɥɶɤɨ ɛɨɥɶɲɟɟ ɤɨɥɢɱɟɫɬɜɨ ɛɟɥɤɨɜɵɯ
ɩɹɬɟɧ, ɱɟɦ ɭ ɨɛɪɚɡɰɚ Ⱥ, ɧɨ ɷɬɨ ɧɟ ɧɟ ɫɨɜɫɟɦ ɭɛɟɞɢɬɟɥɶɧɨ, ɬɚɤ ɤɚɤ ɨɛɳɟɟ ɤɨɥɢɱɟɫɬɜɨ ɩɹɬɟɧ ɫɥɢɲɤɨɦ ɦɚɥɨ.
ɗɬɨ ɧɚɲɥɨ ɫɜɨɟ ɩɨɞɬɜɟɪɠɞɟɧɢɟ ɢ ɩɪɢ ɫɪɚɜɧɟɧɢɢ ɦɨɧɬɚɠɧɵɯ ɢɡɨɛɪɚɠɟɧɢɣ ɩɟɪɜɵɯ ɮɪɚɤɰɢɣ ɨɛɪɚɡɰɚ ɫ CD34+ ɤɥɟɬɤɚɦɢ (ɪɢɫ. 3.13) ɢ ɨɛɪɚɡɰɚ ɫ ɆɇɄ (ɪɢɫ. 3.12). Ɉɱɟɜɢɞɧɨ, ɱɬɨ ɩɹɬɧɚ, ɜɵɹɜɥɟɧɧɵɟ ɩɪɨɝɪɚɦɦɨɣ Phoretix ɞɥɹ ɨɛɪɚɡɰɚ ɫ CD34+ ɤɥɟɬɤɚɦɢ, ɧɚɯɨɞɹɬɫɹ ɧɚ
ɭɪɨɜɧɟ ɧɢɠɧɟɝɨ ɩɪɟɞɟɥɚ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɤɨɥɢɱɟɫɬɜɨ ɛɟɥɤɚ, ɩɪɢɫɭɬɫɬɜɭɸɳɟɝɨ ɜ ɨɛɪɚɡɰɟ ɫ 1×106 CD34 + ɤɥɟɬɨɤ,
ɧɢɠɟ, ɱɟɦ ɜ ɨɛɪɚɡɰɟ ɫ 1×106 ɆɇɄ. Ɉɞɧɚ ɢɡ ɜɨɡɦɨɠɧɵɯ ɩɪɢɱɢɧ ɷɬɨɝɨ – ɩɨɬɟɪɹ ɛɟɥɤɚ ɧɚ ɫɬɚɞɢɹɯ ɩɨɞɝɨɬɨɜɤɢ ɨɛɪɚɡɰɨɜ ɤ ɚɧɚɥɢɡɭ.
Ⱦɚɠɟ ɫ ɭɱɟɬɨɦ ɬɨɝɨ, ɱɬɨ ɤɨɦɩɶɸɬɟɪɧɵɣ ɚɧɚɥɢɡ ɩɨɡɜɨɥɹɟɬ ɨɛɧɚɪɭɠɢɜɚɬɶ ɧɢɡɤɢɟ ɤɨɧɰɟɧɬɪɚɰɢɢ ɢɫɫɥɟɞɭɟɦɵɯ ɫɨɟɞɢɧɟɧɢɣ ɢ ɜɵɹɜɥɹɬɶ ɛɟɥɤɨɜɵɟ ɩɹɬɧɚ, ɨɬɧɨɫɢɬɟɥɶɧɨɟ ɫɨɞɟɪɠɚɧɢɟ ɛɟɥɤɚ ɨɤɚɡɚɥɨɫɶ
ɛɥɢɡɤɢɦ ɤ ɩɨɪɨɝɭ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ, ɱɬɨ ɫɥɟɞɭɟɬ ɢɡ ɦɨɧɬɚɠɧɨɝɨ
ɚɧɚɥɢɡɚ ɝɟɥɟɣ, ɩɪɟɞɫɬɚɜɥɟɧɧɨɝɨ ɧɚ ɪɢɫ. 3.12–3.13.
75
Ȼ.
Ȼ.
Ȼ.
Ȼ.
Ɋɢɫ. 3.11. 2D-ɢɡɨɛɪɚɠɟɧɢɹ CD34+ ȽɋɄ ɱɟɬɵɪɟɯ ɤɥɟɬɨɱɧɵɯ ɮɪɚɤɰɢɣ
(1-ɹ ɮɪɚɤɰɢɹ A. 1-ɹ ɮɪɚɤɰɢɹ Ȼ. 2-ɹ ɮɪɚɤɰɢɹ A. 2-ɹ ɮɪɚɤɰɢɹ Ȼ. 3-ɹ
ɮɪɚɤɰɢɹ Ⱥ. 3-ɹ ɮɪɚɤɰɢɹ Ȼ. 4-ɹ ɮɪɚɤɰɢɹ A. 4-ɹ ɮɪɚɤɰɢɹ Ȼ).
76
Ɋɢɫ. 3.12. ɉɟɪɜɚɹ ɮɪɚɤɰɢɹ CD34+ ȽɋɄ (106 ɤɥɟɬɨɤ) – ɦɨɧɬɚɠɧɚɹ ɜɢɡɭɚɥɢɡɚɰɢɹ
Ɋɢɫ. 3.13. ɉɟɪɜɚɹ ɮɪɚɤɰɢɹ ɆɇɄ (106 ɤɥɟɬɨɤ) – ɦɨɧɬɚɠɧɚɹ ɜɢɡɭɚɥɢɡɚɰɢɹ
77
Ɋɢɫ. 3.14. ɉɟɪɜɚɹ ɮɪɚɤɰɢɹ CD34+ȽɋɄ (2×106 ɤɥɟɬɨɤ) – ɝɟɥɶ ɢ ɟɝɨ ɦɨɧɬɚɠɧɚɹ ɜɢɡɭɚɥɢɡɚɰɢɹ
ɉɨɜɬɨɪɧɵɣ ɚɧɚɥɢɡ ɨɛɪɚɡɰɚ CD34+ȽɋɄ ɛɵɥ ɩɪɨɜɟɞɟɧ ɞɥɹ ɞɜɨɣɧɨɝɨ ɤɨɥɢɱɟɫɬɜɚ (2×106) ɤɥɟɬɨɤ. ɂɡɨɛɪɚɠɟɧɢɹ ɝɟɥɹ ɞɥɹ ɩɟɪɜɨɣ ɮɪɚɤɰɢɢ
ɤɥɟɬɨɤ ɩɪɟɞɫɬɚɜɥɟɧɵ ɧɚ ɪɢɫ. 3.14. Ɉɱɟɜɢɞɧɨ, ɱɬɨ ɪɚɛɨɬɚ ɫ ɞɜɨɣɧɵɦ
ɤɨɥɢɱɟɫɬɜɨɦ ɤɥɟɬɨɤ ɨɛɟɫɩɟɱɢɜɚɥɚ ɩɪɨɬɟɨɦɧɵɣ ɚɧɚɥɢɡ ɞɨɫɬɚɬɨɱɧɵɦ
ɤɨɥɢɱɟɫɬɜɨɦ ɦɚɬɟɪɢɚɥɚ.
78
ɇɚ ɪɢɫ. 3.15–3.16 ɩɪɟɞɫɬɚɜɥɟɧɵ ɨɛɨɛɳɟɧɧɵɟ ɪɟɡɭɥɶɬɚɬɵ ɚɧɚɥɢɡɚ
ɩɪɨɬɟɨɦɧɵɯ ɩɪɨɮɢɥɟɣ ɢ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɛɟɥɤɨɜ ɩɨ ɜɚɠɧɟɣɲɢɦ ɛɟɥɤɚɦ ɬɪɟɯ ɮɪɚɤɰɢɣ CD34+ ȽɋɄ.
1-ɚɹ
ȼɟɪɨɹɬɧɨɫɬɶ ɉɨɤɪɵɬɢɟɉɹɬɧɨ ɂɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟɛɟɥɤɢ
ɋɨɜɩɚɞɟɧɢɹ ɫ ɜɟɪɨɹɬɧɨɫɬɶɸ
ɛɨɥɟɟ 50%
10 ɦɚɤɫɢɦɚɥɶɧɵɯ
ɫɨɜɩɚɞɟɧɢɣ
2-ɚɹ
ȼɟɪɨɹɬɧɨɫɬɶ ɉɨɤɪɵɬɢɟ ɉɹɬɧɨ ɂɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟɛɟɥɤɢ
ɋɨɜɩɚɞɟɧɢɹ ɫ ɜɟɪɨɹɬɧɨɫɬɶɸ
ɛɨɥɟɟ 50%
10 ɦɚɤɫɢɦɚɥɶɧɵɯ
ɫɨɜɩɚɞɟɧɢɣ
3-ɹ
ȼɟɪɨɹɬɧɨɫɬɶɉɨɤɪɵɬɢɟ ɉɹɬɧɨ ɂɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟɛɟɥɤɢ
10 ɦɚɤɫɢɦɚɥɶɧɵɯ
ɫɨɜɩɚɞɟɧɢɣ
ɋɨɜɩɚɞɟɧɢɹ ɫ ɜɟɪɨɹɬɧɨɫɬɶɸ
ɛɨɥɟɟ 50%
Ɋɢɫ. 3.15. ȼɚɠɧɟɣɲɢɟ ɛɟɥɤɨɜɵɟ ɫɬɪɭɤɬɭɪɵ ɞɥɹ ɬɪɟɯ ɮɪɚɤɰɢɣ CD34+ȽɋɄ
(A ɩɨɜɬɨɪɧɨɫɬɶ)
79
1-ɚɹ
ȼɟɪɨɹɬɧɨɫɬɶ ɉɨɤɪɵɬɢɟ
ɉɹɬɧɨ
ɂɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟ ɛɟɥɤɢ
10 ɦɚɤɫɢɦɚɥɶɧɵɯ
ɫɨɜɩɚɞɟɧɢɣ
ɋɨɜɩɚɞɟɧɢɹ ɫ ɜɟɪɨɹɬɧɨɫɬɶɸ
ɛɨɥɟɟ 50%
2-ɚɹ
ȼɟɪɨɹɬɧɨɫɬɶ ɉɨɤɪɵɬɢɟ
ɉɹɬɧɨ
ɂɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟ ɛɟɥɤɢ
10 ɦɚɤɫɢɦɚɥɶɧɵɯ
ɫɨɜɩɚɞɟɧɢɣ
ɋɨɜɩɚɞɟɧɢɹ ɫ ɜɟɪɨɹɬɧɨɫɬɶɸ
ɛɨɥɟɟ 50%
3-ɹ
ȼɟɪɨɹɬɧɨɫɬɶ ɉɨɤɪɵɬɢɟ
10 ɦɚɤɫɢɦɚɥɶɧɵɯ
ɫɨɜɩɚɞɟɧɢɣ
ɉɹɬɧɨ
ɂɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟ ɛɟɥɤɢ
ɋɨɜɩɚɞɟɧɢɹ ɫ ɜɟɪɨɹɬɧɨɫɬɶɸ
ɛɨɥɟɟ 50%
Ɋɢɫ. 3.16. ȼɚɠɧɟɣɲɢɟ ɛɟɥɤɨɜɵɟ ɫɬɪɭɤɬɭɪɵ ɞɥɹ ɬɪɟɯ ɮɪɚɤɰɢɣ CD34+
ȽɋɄ (Ȼ ɩɨɜɬɨɪɧɨɫɬɶ)
ɉɪɢɱɢɧɚ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɧɚɦɢ 50%-ɤɪɢɬɟɪɢɹ (ɜɟɪɨɹɬɧɨɫɬɧɨɝɨ ɤɨɷɮɮɢɰɢɟɧɬɚ ɞɨɫɬɨɜɟɪɧɨɫɬɢ – ɩɪɨɰɟɧɬɧɨɝɨ ɩɨɤɪɵɬɢɹ ɚɦɢɧɨɤɢɫɥɨɬɧɨɣ
ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɢ ɛɟɥɤɚ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɦɢ ɩɟɩɬɢɞɚɦɢ) ɢɥɢ
ɞɚɠɟ ɛɨɥɟɟ ɡɧɚɱɢɦɨɝɨ ɨɛɴɹɫɧɹɟɬɫɹ ɬɟɦ, ɱɬɨ ɱɟɦ ɜɵɲɟ ɞɚɧɧɚɹ ɜɟɥɢɱɢɧɚ, ɬɟɦ ɞɨɫɬɨɜɟɪɧɟɟ ɢɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ. ɗɬɨ ɹɜɥɹɟɬɫɹ ɦɟɪɨɣ ɭɜɟɪɟɧɧɨɫɬɢ ɜ ɬɨɦ, ɱɬɨ id ɛɟɥɤɚ ɹɜɥɹɟɬɫɹ ɜɟɥɢɱɢɧɨɣ ɢɫɬɢɧɧɨɣ (ɫ ɜɟɪɨɹɬɧɨɫɬɶɸ >50%), ɚ ɧɟ ɨɲɢɛɨɱɧɨɣ.
80
ȼɚɠɧɟɣɲɢɟ ɛɟɥɤɨɜɵɟ ɫɬɪɭɤɬɭɪɵ (ɜɟɪɨɹɬɧɨɫɬɧɵɣ ɤɨɷɮɮɢɰɢɟɧɬ
ɞɨɫɬɨɜɟɪɧɨɫɬɢ 50% ɢ ɜɵɲɟ), ɜɵɪɚɠɟɧɧɵɟ ɤɚɤ ɤɨɥɢɱɟɫɬɜɨ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɯ ɜ ɪɚɡɧɵɯ ɫɬɪɭɤɬɭɪɚɯ ɤɥɟɬɤɢ ɛɟɥɤɨɜ, ɢɫɩɨɥɶɡɨɜɚɧɵ ɞɥɹ ɢɥɥɸɫɬɪɚɰɢɢ ɜ ɤɚɱɟɫɬɜɟ ɩɪɢɦɟɪɚ ɚɧɚɥɢɡɚ, ɤɨɬɨɪɵɣ ɦɨɠɟɬ ɛɵɬɶ ɜɵɩɨɥɧɟɧ ɡɚ
ɫɱɟɬ ɨɛɴɟɞɢɧɟɧɢɹ ɪɟɡɭɥɶɬɚɬɨɜ ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɢ (ɪɢɫ. 3.17–3.18).
Ɋɢɫ. 3.17. ȼɚɠɧɟɣɲɢɟ ɛɟɥɤɨɜɵɟ ɫɬɪɭɤɬɭɪɵ ɜ ɬɟɪɦɢɧɚɯ ɤɥɟɬɨɱɧɨɣ ɤɨɦɩɚɪɬɦɟɧɬɚɥɢɡɚɰɢɢ. Ƚɪɚɮɢɱɟɫɤɨɟ ɩɪɟɞɫɬɚɜɥɟɧɢɟ ɨɬɧɨɫɢɬɟɥɶɧɨɣ ɥɨɤɚɥɢɡɚɰɢɢ ɛɟɥɤɨɜ ɜ ȽɋɄ
Ɋɢɫ. 3.18. ȼɚɠɧɟɣɲɢɟ ɛɟɥɤɨɜɵɟ ɫɬɪɭɤɬɭɪɵ ɜ ɬɟɪɦɢɧɚɯ ɤɥɟɬɨɱɧɨɣ ɤɨɦɩɚɪɬɦɟɧɬɚɥɢɡɚɰɢɢ. ɋɯɟɦɚɬɢɱɟɫɤɨɟ ɩɪɟɞɫɬɚɜɥɟɧɢɟ ɨɬɧɨɫɢɬɟɥɶɧɨɣ ɥɨɤɚɥɢɡɚɰɢɢ ɛɟɥɤɨɜ ɜ ȽɋɄ.
81
Ʉɚɤ ɩɨɥɚɝɚɟɬ Tao [86], ɭ ȽɋɄ ɛɟɥɤɢ ɥɨɤɚɥɢɡɨɜɚɧɵ ɜ ɨɫɧɨɜɧɨɦ ɜɨɤɪɭɝ ɹɞɪɚ ɢ ɜ ɰɢɬɨɩɥɚɡɦɚɬɢɱɟɫɤɨɦ ɞɨɦɟɧɟ. ɗɬɨ ɫɨɨɬɜɟɬɫɬɜɭɟɬ ɝɢɩɨɬɟɡɟ, ɱɬɨ ɧɟɡɪɟɥɵɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ ɚɤɬɢɜɧɨ ɜɨɜɥɟɤɚɸɬɫɹ ɜ ɫɢɧɬɟɡ ɛɟɥɤɚ ɢ, ɤɚɤ ɪɟɡɭɥɶɬɚɬ, ɚɤɤɭɦɭɥɢɪɭɸɬ ɛɨɥɶɲɢɟ ɤɨɥɢɱɟɫɬɜɚ ɛɟɥɤɚ ɪɹɞɨɦ ɫ
ɬɪɚɧɫɥɹɰɢɨɧɧɵɦɢ ɡɨɧɚɦɢ ɤɥɟɬɤɢ. Ʉɨɧɟɱɧɨ, ɞɥɹ ɩɨɞɬɜɟɪɠɞɟɧɢɹ ɷɬɨɣ
ɝɢɩɨɬɟɡɵ ɬɪɟɛɭɸɬɫɹ ɞɨɩɨɥɧɢɬɟɥɶɧɵɟ ɢɫɫɥɟɞɨɜɚɧɢɹ, ɧɨ ɩɟɪɜɵɣ ɲɚɝ ɜ
ɷɬɨɦ ɧɚɩɪɚɜɥɟɧɢɢ ɭɠɟ ɫɞɟɥɚɧ ɫ ɩɨɦɨɳɶɸ ɢɦɟɧɧɨ ɩɪɨɬɟɨɦɢɤɢ.
3.3. ɂɡɭɱɟɧɢɟ ɚɫɫɨɰɢɚɰɢɢ ɩɪɨɬɟɨɦɢɱɟɫɤɨɝɨ ɩɪɨɮɢɥɹ ɫ ɚɬɟɪɨɫɤɥɟɪɨɡɨɦ
Ɉɱɟɜɢɞɧɨ, ɱɬɨ ɜɵɹɜɥɟɧɢɟ ɮɭɧɤɰɢɨɧɚɥɶɧɨɣ ɫɜɹɡɢ ɦɟɠɞɭ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɦɢ ɩɨɪɚɠɟɧɢɹɦɢ ɢ ɩɪɨɬɟɨɦɢɱɟɫɤɢɦ ɩɪɨɮɢɥɟɦ ɢɧɬɢɦɵ
ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ ɢɦɟɟɬ ɢɫɤɥɸɱɢɬɟɥɶɧɨɟ ɡɧɚɱɟɧɢɟ ɞɥɹ ɩɨɧɢɦɚɧɢɹ ɢɧɢɰɢɢɪɭɸɳɢɯ ɩɪɢɱɢɧ ɜɨɡɧɢɤɧɨɜɟɧɢɹ ɚɬɟɪɨɫɤɥɟɪɨɡɚ. ɍɠɟ ɫɨɡɞɚɧɵ ɛɚɡɵ
ɞɚɧɧɵɯ ɩɨ ɫɨɬɧɹɦ ɛɟɥɤɨɜ ɩɪɨɬɟɨɦɚ ɦɢɨɤɚɪɞɚ, ɭɪɨɜɧɢ ɤɨɬɨɪɵɯ ɢɡɦɟɧɹɸɬɫɹ ɩɪɢ ɫɟɪɞɟɱɧɨ-ɫɨɫɭɞɢɫɬɨɣ ɩɚɬɨɥɨɝɢɢ, ɤɚɤ ɨɫɬɪɨɣ, ɬɚɤ ɢ ɯɪɨɧɢɱɟɫɤɨɣ
[17]. Ɉɞɧɚɤɨ ɞɨ ɧɚɫɬɨɹɳɟɝɨ ɜɪɟɦɟɧɢ ɥɢɲɶ ɜ ɨɱɟɧɶ ɧɟɛɨɥɶɲɨɦ ɤɨɥɢɱɟɫɬɜɟ ɪɚɛɨɬ ɛɵɥɢ ɢɫɫɥɟɞɨɜɚɧɵ ɛɟɥɤɢ, ɜɵɞɟɥɟɧɧɵɟ ɢɡ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɛɥɹɲɟɤ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ [29, 31, 56]. Ɉɫɨɛɵɣ ɢɧɬɟɪɟɫ ɩɪɢ ɩɪɨɜɟɞɟɧɢɢ ɧɚɲɟɝɨ ɢɫɫɥɟɞɨɜɚɧɢɹ ɩɪɟɞɫɬɚɜɥɹɥɢ ɩɪɨɬɟɨɦɧɵɟ ɩɪɨɮɢɥɢ ɢɧɬɢɦɵ ɢ
ɦɟɞɢɢ ɚɪɬɟɪɢɣ ɩɪɢ ɪɚɡɧɵɯ ɫɬɚɞɢɹɯ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ ɩɨɪɚɠɟɧɢɹ.
ɇɚ ɪɢɫ. 3.19 ɩɪɟɞɫɬɚɜɥɟɧɵ 2D-ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦɵ ɷɤɫɬɪɚɤɬɨɜ
ɛɟɥɤɚ ɢɡ ɨɛɪɚɡɰɨɜ ɬɤɚɧɢ ɧɟɩɨɪɚɠɟɧɧɨɣ ɢɧɬɢɦɵ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ ɢ ɥɢɩɨɮɢɛɪɨɡɧɨɣ ɛɥɹɲɤɢ, ɩɨɥɭɱɟɧɧɵɯ ɢɡ ɨɞɧɨɝɨ ɚɭɬɨɩɫɢɣɧɨɝɨ ɦɚɬɟɪɢɚɥɚ.
Ɉɱɟɜɢɞɧɨ, ɱɬɨ ɩɨɥɭɱɟɧɧɵɟ ɩɪɨɬɟɨɦɧɵɟ ɩɪɨɮɢɥɢ ɢɦɟɸɬ ɫɭɳɟɫɬɜɟɧɧɵɟ ɤɚɱɟɫɬɜɟɧɧɵɟ ɢ ɤɨɥɢɱɟɫɬɜɟɧɧɵɟ ɪɚɡɥɢɱɢɹ. ȼ ɱɚɫɬɧɨɫɬɢ, ɜ ɥɢɩɨɮɢɛɪɨɡɧɨɣ ɛɥɹɲɤɟ (ɧɚɢɛɨɥɟɟ ɚɤɬɢɜɧɨɣ ɢ ɭɝɪɨɠɚɸɳɟɣ ɠɢɡɧɢ ɮɨɪɦɟ
ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ ɩɨɪɚɠɟɧɢɹ) ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɧɨɪɦɨɣ ɨɬɦɟɱɚɟɬɫɹ
82
ɩɪɟɨɛɥɚɞɚɧɢɟ ɛɟɥɤɨɜ ɫ ɦɚɫɫɨɣ 75-90 ɤȾɚ ɢ ɢɡɨɷɥɟɤɬɪɢɱɟɫɤɨɣ ɬɨɱɤɨɣ ɜ
ɢɧɬɟɪɜɚɥɟ pH ɨɬ 5 ɞɨ 7; ɛɟɥɤɨɜ ɫ ɦɚɫɫɨɣ ɨɤɨɥɨ 65 ɤȾɚ ɢ ɢɡɨɷɥɟɤɬɪɢɱɟɫɤɨɣ ɬɨɱɤɨɣ ɜ ɢɧɬɟɪɜɚɥɟ ɪɇ ɨɬ 4,5 ɞɨ 5,5. ɉɪɢ ɷɬɨɦ ɜ ɥɢɩɨɮɢɛɪɨɡɧɨɣ
ɛɥɹɲɤɟ ɭɦɟɧɶɲɟɧɨ ɫɨɞɟɪɠɚɧɢɟ ɛɟɥɤɨɜ ɫ ɦɚɫɫɨɣ ɨɤɨɥɨ 70 ɤȾɚ ɢ ɨɤɨɥɨ
40 ɤȾɚ ɢ ɢɡɨɷɥɟɤɬɢɱɟɫɤɨɣ ɬɨɱɤɨɣ ɜ ɢɧɬɟɪɜɚɥɟ ɪɇ ɨɬ 4,5 ɞɨ 5,0. Ɍɚɤɠɟ
ɫɭɳɟɫɬɜɭɸɬ ɦɧɨɝɨɱɢɫɥɟɧɧɵɟ ɦɟɧɟɟ ɜɵɪɚɠɟɧɧɵɟ ɪɚɡɥɢɱɢɹ.
ɇɚ ɪɢɫ. 3.20 ɩɪɟɞɫɬɚɜɥɟɧɵ ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦɵ ɷɤɫɬɪɚɤɬɨɜ ɛɟɥɤɚ ɢɡ
ɨɛɪɚɡɰɨɜ ɬɤɚɧɢ ɢɧɬɢɦɵ, ɩɨɥɭɱɟɧɧɨɣ ɢɡ ɚɭɬɨɩɫɢɣɧɨɝɨ ɦɚɬɟɪɢɚɥɚ, ɜ ɤɨɬɨɪɨɦ ɩɪɢɫɭɬɫɬɜɨɜɚɥɢ, ɧɚɪɹɞɭ ɫ ɧɟɩɨɪɚɠɟɧɧɵɦɢ ɭɱɚɫɬɤɚɦɢ, ɜɫɟ ɢɡɭɱɚɟɦɵɟ ɜɢɞɵ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɩɨɪɚɠɟɧɢɣ (ɧɚɱɚɥɶɧɵɟ ɩɨɪɚɠɟɧɢɹ, ɠɢɪɨɜɚɹ ɩɨɥɨɫɚ, ɥɢɩɨɮɢɛɪɨɡɧɚɹ ɛɥɹɲɤɚ, ɮɢɛɪɨɡɧɚɹ ɛɥɹɲɤɚ). Ɉɱɟɜɢɞɧɨ,
ɱɬɨ ɫɭɳɟɫɬɜɟɧɧɵɟ ɢɡɦɟɧɟɧɢɹ ɜ ɩɪɨɬɟɨɦɧɨɦ ɩɪɨɮɢɥɟ ɩɪɨɢɫɯɨɞɹɬ ɭɠɟ ɧɚ
ɫɚɦɵɯ ɪɚɧɧɢɯ ɫɬɚɞɢɹɯ ɮɨɪɦɢɪɨɜɚɧɢɹ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ ɩɨɪɚɠɟɧɢɹ,
ɬɨ ɟɫɬɶ ɩɪɢ ɠɢɪɨɜɨɣ ɢɧɮɢɥɶɬɪɚɰɢɢ. Ɇɚɤɪɨɫɤɨɩɢɱɟɫɤɢ ɧɚɱɚɥɶɧɵɟ ɩɨɪɚɠɟɧɢɹ ɩɪɟɞɫɬɚɜɥɹɸɬ ɫɨɛɨɣ ɭɱɚɫɬɤɢ ɫ ɝɥɚɞɤɨɣ ɠɟɥɬɨɜɚɬɨɣ ɩɨɜɟɪɯɧɨɫɬɶɸ,
ɢɧɨɝɞɚ ɫ ɦɟɥɤɢɦɢ ɠɟɥɬɵɦɢ ɬɨɱɤɚɦɢ; ɦɢɤɪɨɫɤɨɩɢɱɟɫɤɢɟ ɢɡɦɟɧɟɧɢɹ ɩɪɢ
ɷɬɨɦ ɦɢɧɢɦɚɥɶɧɵ: ɧɚɛɥɸɞɚɸɬɫɹ ɧɟɛɨɥɶɲɢɟ ɧɚɤɨɩɥɟɧɢɹ ɜɧɟɤɥɟɬɨɱɧɵɯ
ɥɢɩɢɞɧɵɯ ɤɚɩɟɥɶ ɜ ɫɨɟɞɢɧɢɬɟɥɶɧɨ-ɬɤɚɧɧɨɦ ɦɚɬɪɢɤɫɟ. ɋɱɢɬɚɸɬ, ɱɬɨ ɜ
ɭɱɚɫɬɤɚɯ ɧɚɱɚɥɶɧɵɯ ɩɨɪɚɠɟɧɢɣ, ɩɨɦɢɦɨ ɨɫɟɞɥɵɯ ɤɥɟɬɨɤ, ɨɬɦɟɱɚɟɬɫɹ
ɧɟɫɤɨɥɶɤɨ ɭɜɟɥɢɱɟɧɧɨɟ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɧɟɩɨɪɚɠɟɧɧɨɣ ɢɧɬɢɦɨɣ ɤɨɥɢɱɟɫɬɜɨ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɤɥɟɬɨɤ; ɩɪɢ ɷɬɨɦ ɨɬɫɭɬɫɬɜɭɸɬ ɹɜɧɵɟ ɧɚɪɭɲɟɧɢɹ ɜ
ɫɬɪɭɤɬɭɪɟ ɬɤɚɧɢ. ɉɪɢ ɷɬɨɦ ɩɪɨɬɟɨɦɧɵɣ ɩɪɨɮɢɥɶ ɬɤɚɧɢ ɭɠɟ ɫɭɳɟɫɬɜɟɧɧɨ
ɢɡɦɟɧɟɧ. ɇɟɫɦɨɬɪɹ ɧɚ ɫɭɳɟɫɬɜɟɧɧɵɟ ɦɨɪɮɨɥɨɝɢɱɟɫɤɢɟ ɢɡɦɟɧɟɧɢɹ, ɩɪɨɢɫɯɨɞɹɳɢɟ ɩɪɢ ɩɪɨɝɪɟɫɫɢɪɨɜɚɧɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ (ɮɨɪɦɢɪɨɜɚɧɢɟ ɠɢɪɨɜɵɯ ɩɨɥɨɫ, ɥɢɩɨɮɢɛɪɨɡɧɵɯ ɢ ɮɢɛɪɨɡɧɵɯ ɛɥɹɲɟɤ – ɧɚɤɨɩɥɟɧɢɟ ɜɧɭɬɪɢɤɥɟɬɨɱɧɵɯ ɢ ɜɧɟɤɥɟɬɨɱɧɵɯ ɥɢɩɢɞɨɜ, ɪɚɡɪɚɫɬɚɧɢɟ ɫɨɟɞɢɧɢɬɟɥɶɧɨɬɤɚɧɧɨɝɨ ɦɚɬɪɢɤɫɚ, ɢɡɦɟɧɟɧɢɟ ɤɥɟɬɨɱɧɨɝɨ ɫɨɫɬɚɜɚ ɬɤɚɧɢ, ɮɨɪɦɢɪɨɜɚɧɢɟ ɜɨɡ-
83
ɜɵɲɚɸɳɢɯɫɹ ɩɨɪɚɠɟɧɢɣ), ɩɪɢɧɰɢɩɢɚɥɶɧɵɯ ɢɡɦɟɧɟɧɢɣ ɩɪɨɬɟɨɦɧɨɝɨ
ɩɪɨɮɢɥɹ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɧɚɱɚɥɶɧɵɦɢ ɩɨɪɚɠɟɧɢɹɦɢ ɭɠɟ ɧɟ ɩɪɨɢɫɯɨɞɢɬ.
ɋɱɢɬɚɟɬɫɹ, ɱɬɨ ɩɪɢ ɚɬɟɪɨɫɤɥɟɪɨɡɟ ɨɫɧɨɜɧɵɟ ɩɚɬɨɥɨɝɢɱɟɫɤɢɟ ɢɡɦɟɧɟɧɢɹ ɩɪɨɢɫɯɨɞɹɬ ɜ ɢɧɬɢɦɟ ɚɪɬɟɪɢɣ ɤɚɤ ɦɨɪɮɨɥɨɝɢɱɟɫɤɨɦ ɫɭɛɫɬɪɚɬɟ ɞɥɹ
ɮɨɪɦɢɪɨɜɚɧɢɹ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɩɨɪɚɠɟɧɢɣ, ɚ ɜ ɦɟɞɢɚɥɶɧɨɦ ɫɥɨɟ
ɧɚɛɥɸɞɚɸɬɫɹ ɜɬɨɪɢɱɧɵɟ ɢɡɦɟɧɟɧɢɹ. Ⱦɥɹ ɨɰɟɧɤɢ ɬɚɤɢɯ ɢɡɦɟɧɟɧɢɣ ɛɵɥɨ
ɩɪɨɜɟɞɟɧɨ ɢɡɭɱɟɧɢɟ ɩɪɨɬɟɨɦɧɨɝɨ ɩɪɨɮɢɥɹ ɭɱɚɫɬɤɨɜ ɦɟɞɢɢ, ɩɨɞɥɟɠɚɳɢɯ
ɩɨɞ ɧɟɢɡɦɟɧɟɧɧɨɣ ɢɧɬɢɦɨɣ ɢ ɩɨɞ ɥɢɩɨɮɢɛɪɨɡɧɨɣ ɛɥɹɲɤɨɣ (ɪɢɫ. 3.22).
Ɉɱɟɜɢɞɧɨ, ɱɬɨ ɜ ɦɟɞɢɢ ɬɚɤɠɟ ɩɪɨɢɫɯɨɞɹɬ ɫɭɳɟɫɬɜɟɧɧɵɟ ɢɡɦɟɧɟɧɢɹ ɩɪɨɬɟɨɦɧɨɝɨ ɩɪɨɮɢɥɹ, ɚɫɫɨɰɢɢɪɨɜɚɧɧɵɟ ɫ ɧɚɥɢɱɢɟɦ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ
ɩɨɪɚɠɟɧɢɹ. Ʉɥɸɱɟɜɵɟ ɪɚɡɥɢɱɢɹ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ, ɜɵɹɜɥɟɧɧɵɟ ɧɚ ɞɚɧɧɵɯ
ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦɚɯ, ɩɪɢɜɟɞɟɧɵ ɜ ɬɚɛɥ. 3.2 (ɮɪɚɝɦɟɧɬɵ ɮɨɬɨ). ɇɚ
ɪɢɫ. 3.21 ɩɪɟɞɫɬɚɜɥɟɧɨ ɮɨɬɨ ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦɵ ɷɤɫɬɪɚɤɬɚ ɛɟɥɤɨɜ ɢɡ
ɦɟɞɢɢ, ɩɨɞɥɟɠɚɳɟɣ ɩɨɞ ɧɟɩɨɪɚɠɟɧɧɵɦ ɭɱɚɫɬɤɨɦ ɢɧɬɢɦɵ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ. ɋɬɪɟɥɤɚɦɢ ɭɤɚɡɚɧɵ ɛɟɥɤɨɜɵɟ ɩɹɬɧɚ ɜ ɨɛɥɚɫɬɢ ɛɟɥɤɨɜ ɦɚɫɫɨɣ
ɦɟɧɟɟ 33 ɤȾɚ, ɞɥɹ ɤɨɬɨɪɵɯ ɧɚɛɥɸɞɚɸɬɫɹ ɧɚɢɛɨɥɟɟ ɜɵɪɚɠɟɧɧɵɟ ɤɨɥɢɱɟɫɬɜɟɧɧɵɟ ɢɡɦɟɧɟɧɢɹ ɩɪɢ ɚɧɚɥɢɡɟ ɭɱɚɫɬɤɨɜ ɦɟɞɢɢ, ɩɨɞɥɟɠɚɳɢɯ ɩɨɞ
ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɦɢ ɩɨɪɚɠɟɧɢɹɦɢ (ɥɢɩɨɮɢɛɪɨɡɧɵɦɢ ɢ ɮɢɛɪɨɡɧɵɦɢ
ɛɥɹɲɤɚɦɢ). Ȼɵɥɚ ɩɪɟɞɩɪɢɧɹɬɚ ɩɨɩɵɬɤɚ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɞɚɧɧɵɯ ɛɟɥɤɨɜ
ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɬɟɯɧɨɥɨɝɢɢ MALDI-TOF ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɢ. Ɋɟɡɭɥɶɬɚɬɵ ɚɧɚɥɢɡɚ ɩɪɟɞɫɬɚɜɥɟɧɵ ɜ ɬɚɛɥ. 3.3. ɗɬɢ ɧɢɡɤɨɦɨɥɟɤɭɥɹɪɧɵɟ ɛɟɥɤɢ
ɨɤɚɡɚɥɢɫɶ ɮɪɚɝɦɟɧɬɚɦɢ ɢɡɨɮɨɪɦɵ 1 ɚɧɧɟɤɫɢɧɚ-2, ɚɥɶɮɚ-ȼ-ɤɪɢɫɬɚɥɥɢɧɚ,
r-ras ɨɧɤɨɝɟɧɚ, ɛɟɥɤɚ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ ɛɟɬɚ-1, ɛɟɬɚɝɥɨɛɢɧɚ, ɬɪɚɧɫɝɟɥɢɧɚ ɢ
ɟɝɨ ɢɡɨɮɨɪɦ, ɚ ɬɚɤɠɟ ɩɟɪɨɤɫɢɪɟɞɨɤɫɢɧɚ-1.
ɋɥɟɞɭɟɬ ɨɬɦɟɬɢɬɶ, ɱɬɨ ɞɚɧɧɵɣ ɚɧɚɥɢɡ ɧɨɫɢɥ ɜɟɫɶɦɚ ɨɝɪɚɧɢɱɟɧɧɵɣ ɯɚɪɚɤɬɟɪ. ɂɡ-ɡɚ ɫɥɨɠɧɨɫɬɢ ɩɪɨɰɟɞɭɪɵ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɧɚ ɞɚɧɧɨɦ
ɷɬɚɩɟ ɢɫɫɥɟɞɨɜɚɧɢɹ ɧɟ ɛɵɥɢ ɜɤɥɸɱɟɧɵ ɛɟɥɤɢ ɫ ɦɨɥɟɤɭɥɹɪɧɨɣ ɦɚɫɫɨɣ
ɛɨɥɟɟ 40 ɤȾɚ, ɯɨɬɹ ɢɡ ɪɟɡɭɥɶɬɚɬɨɜ 2D ɷɥɟɤɬɪɨɮɨɪɟɡɚ, ɩɪɟɞɫɬɚɜɥɟɧɧɵɯ
84
ɧɚ ɪɢɫ. 3.19–3.22, ɨɱɟɜɢɞɧɨ, ɱɬɨ ɜ ɷɬɨɦ ɞɢɚɩɚɡɨɧɟ ɦɨɥɟɤɭɥɹɪɧɵɯ ɦɚɫɫ
ɩɪɢ ɪɚɡɜɢɬɢɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɩɨɪɚɠɟɧɢɣ ɬɚɤɠɟ ɩɪɨɢɫɯɨɞɹɬ ɫɭɳɟɫɬɜɟɧɧɵɟ ɢɡɦɟɧɟɧɢɹ ɩɪɨɬɟɨɦɧɨɝɨ ɩɪɨɮɢɥɹ ɤɚɤ ɜ ɢɧɬɢɦɚɥɶɧɨɦ, ɬɚɤ
ɢ ɦɟɞɢɚɥɶɧɨɦ ɫɥɨɟ ɚɨɪɬɵ.
Ɍɚɛɥɢɰɚ 3.2. Ɏɪɚɝɦɟɧɬɵ ɞɜɭɦɟɪɧɵɯ ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦ ɛɟɥɤɨɜ
ɦɟɞɢɢ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ
ɍɱɚɫɬɨɤ ɩɨɞ ɧɟɩɨɪɚɠɟɧɧɨɣ ɢɧɬɢɦɨɣ
ɍɱɚɫɬɨɤ ɩɨɞ ɥɢɩɨɮɢɛɪɨɡɧɨɣ ɛɥɹɲɤɨɣ
Ɋɚɡɥɢɱɢɹ
ɂɫɱɟɡɧɨɜɟɧɢɟ
ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ
29 ɤȾɚ
ɉɨɹɜɥɟɧɢɟ ɩɹɬɧɚ
26 ɤȾɚ,
ɢɫɱɟɡɧɨɜɟɧɢɹ
ɩɹɬɧɚ 27 ɤȾɚ
Ʉɨɥɢɱɟɫɬɜɟɧɧɵɟ
ɢɡɦɟɧɟɧɢɹ
ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ
17 ɤȾɚ
ɂɫɱɟɡɧɨɜɟɧɢɟ
ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ
19 ɤȾɚ,
ɤɨɥɢɱɟɫɬɜɟɧɧɵɟ
ɢɡɦɟɧɟɧɢɹ ɞɪɭɝɢɯ
ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ
Ʉɨɥɢɱɟɫɬɜɟɧɧɵɟ
ɢɡɦɟɧɟɧɢɹ
ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ
24 ɤȾɚ
85
Ɍɚɛɥɢɰɚ 3.3. Ɋɟɡɭɥɶɬɚɬɵ ɢɞɟɧɬɢɮɢɤɚɰɢɢ ɩɹɬɟɧ ɛɟɥɤɨɜ ɢɡ 2D ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦ ɛɟɥɤɨɜ ɦɟɞɢɢ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ
ʋ
Ȼɟɥɨɤ
ɇɨɦɟɪ
ɜ NCBI
protein
ȼɟɪɨɹɬɧɨɫɬɧɵɣ
%
ɤɨɷɮɮɢɰɢɟɧɬ ɞɨɫɩɟɪɟɬɨɜɟɪɧɨɫɬɢ / ɤɨɥɢɤɪɵɱɟɫɬɜɨ ɜɵɹɜɥɟɧɬɢɹ
ɧɵɯ ɦɚɫɫ ɩɟɩɬɢɞɨɜ
Mw/pI
ɷɤɫɩ.
Mw/pI
ɬɟɨɪ.
6
Ⱥɧɧɟɤɫɢɧ-2, ɢɡɨɮɨɪ50845388
ɦɚ 1 (ɮɪɚɝɦɟɧɬ)
Ⱥɥɶɮɚ-ȼ-ɤɪɢɫɬɚɥɥɢɧ 4503057
r-ras ɨɧɤɨɝɟɧ
5454028
Ȼɟɥɨɤ ɬɟɩɥɨɜɨɝɨ
4504517
ɲɨɤɚ ɛɟɬɚ-1
Ȼɟɥɨɤ ɬɟɩɥɨɜɨɝɨ
4504517
ɲɨɤɚ ɛɟɬɚ-1
ɐɟɩɶ Ⱥ ɝɟɦɨɝɥɨɛɢɧɚ 61679690
7
Ȼɟɬɚ ɝɥɨɛɢɧ
71727231
117/7
60
16,0/7,80 16,0/7,86
8
Ɍɪɚɧɫɝɟɥɢɧ
48255905
89/10
50
22,6/8,87
9
Ɍɪɚɧɫɝɟɥɢɧ
48255905
206/22
83
22,6/8,87
10 Ɍɪɚɧɫɝɟɥɢɧ
48255905
145/10
53
22,6/8,87
122/10, 53/5
52, 27
22,6/8,87
147/12
47
22,6/8,87
1
2
3
4
5
ɋɦɟɫɶ ɬɪɚɧɫɝɟɥɢɧɚ ɢ 48255905,
11
ɩɟɪɨɤɫɢɪɟɞɨɤɫɢɧɚ-1 55959887
74/11
35
35,0/7,25 40,4/8,53
62/5
117/8
23
45
19,5/7,30 20,1/6,76
22,5/6,50 23,5/6,44
97/10
52
23,0/5,60 22,8/5,98
97/10
25
23,0/5,80 22,8/5,98
68/8
64
15,5/8,30 15,1/8,72
12 Ɍɪɚɧɫɝɟɥɢɧ
48255905
13 Ɍɪɚɧɫɝɟɥɢɧ
48255905
106/8
37
22,6/8,87
14 Ɍɪɚɧɫɝɟɥɢɧ
48255905
142/10
45
22,6/8,87
15 Ɍɪɚɧɫɝɟɥɢɧ
48255905
172/21
73
22,6/8,87
16 Ɍɪɚɧɫɝɟɥɢɧ
48255905
Ɍɪɚɧɫɝɟɥɢɧ, ɢɡɨɮɨɪ17
119587704
ɦɚ CRA_c
18 Ⱥɥɶɮɚ-ȼ-ɤɪɢɫɬɚɥɥɢɧ 4503057
143/17
64
22,6/8,87
55/6
33
23,7/8,54
62/5
26
20,1/6,76
19 Ɍɪɚɧɫɝɟɥɢɧ ɜɚɪɢɚɧɬ
62897565
67/6
23
20,9/8,69
20 Ɍɪɚɧɫɝɟɥɢɧ ɜɚɪɢɚɧɬ
62897565
54/5
28
20,9/8,69
ɉɪɢɦɟɱɚɧɢɟ: ɩɪɢɜɟɞɟɧɵ ɪɟɡɭɥɶɬɚɬɵ ɤɨɦɩɶɸɬɟɪɧɨɝɨ ɩɨɢɫɤɚ ɩɨ ɛɚɡɚɦ
ɞɚɧɧɵɯ
ɨ
ɫɟɤɜɟɧɢɪɨɜɚɧɧɵɯ
ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɹɯ
(NCBI,
www.ncbi.nlm.nih.gov) - ɩɪɨɰɟɧɬ ɫɨɜɩɚɞɟɧɢɹ ɜɵɹɜɥɟɧɧɵɯ ɦɚɫɫ ɬɪɢɩɬɢɱɟɫɤɢɯ ɩɟɩɬɢɞɨɜ ɫ ɚɦɢɧɨɤɢɫɥɨɬɧɨɣ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɶɸ ɫɨɨɬɜɟɬɫɬɜɭɸɳɟɝɨ ɛɟɥɤɚ
86
Ɋɢɫ. 3.19. 2D ɷɥɟɤɬɪɨɮɨɪɟɡ ɷɤɫɬɪɚɤɬɨɜ ɛɟɥɤɨɜ ɢɡ ɢɧɬɢɦɵ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ.
ɋɥɟɜɚ – ɧɟɩɨɪɚɠɟɧɧɚɹ ɢɧɬɢɦɚ ɚɨɪɬɵ, ɫɩɪɚɜɚ – ɥɢɩɨɮɢɛɪɨɡɧɚɹ ɛɥɹɲɤɚ.
Ɉɤɪɚɫɤɚ ɫɟɪɟɛɪɨɦ
Ɋɢɫ. 3.20. 2D ɷɥɟɤɬɪɨɮɨɪɟɡ ɷɤɫɬɪɚɤɬɨɜ ɛɟɥɤɨɜ ɢɡ ɢɧɬɢɦɵ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ. ȼɜɟɪɯɭ ɫɥɟɜɚ – ɧɟɩɨɪɚɠɟɧɧɚɹ ɢɧɬɢɦɚ ɚɨɪɬɵ, ɜɜɟɪɯɭ ɩɨɫɟɪɟɞɢɧɟ –
ɠɢɪɨɜɚɹ ɢɧɮɢɥɶɬɪɚɰɢɹ (ɧɚɱɚɥɶɧɵɟ ɩɨɪɚɠɟɧɢɹ), ɜɜɟɪɯɭ ɫɩɪɚɜɚ – ɠɢɪɨɜɚɹ ɩɨɥɨɫɚ, ɜɧɢɡɭ ɫɥɟɜɚ - ɥɢɩɨɮɢɛɪɨɡɧɚɹ ɛɥɹɲɤɚ, ɜɧɢɡɭ ɫɩɪɚɜɚ – ɮɢɛɪɨɡɧɚɹ ɛɥɹɲɤɚ. Ɉɤɪɚɫɤɚ ɫɟɪɟɛɪɨɦ
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Ɋɢɫ. 3.21. 2D ɷɥɟɤɬɪɨɮɨɪɟɡ ɷɤɫɬɪɚɤɬɨɜ ɛɟɥɤɨɜ ɢɡ ɭɱɚɫɬɤɚ ɦɟɞɢɢ ɚɨɪɬɵ
ɱɟɥɨɜɟɤɚ, ɩɨɞɥɟɠɚɳɟɝɨ ɩɨɞ ɧɟɩɨɪɚɠɟɧɧɵɦ ɭɱɚɫɬɤɨɦ ɢɧɬɢɦɵ (ɫɥɟɜɚ) ɢ
ɩɨɞ ɥɢɩɨɮɢɛɪɨɡɧɨɣ ɛɥɹɲɤɨɣ (ɫɩɪɚɜɚ). Ɉɤɪɚɫɤɚ ɫɟɪɟɛɪɨɦ
Ɋɢɫ. 3.22. 2D ɷɥɟɤɬɪɨɮɨɪɟɡ ɷɤɫɬɪɚɤɬɚ ɛɟɥɤɨɜ ɢɡ ɭɱɚɫɬɤɚ ɦɟɞɢɢ ɚɨɪɬɵ
ɱɟɥɨɜɟɤɚ, ɩɨɞɥɟɠɚɳɟɝɨ ɩɨɞ ɧɟɩɨɪɚɠɟɧɧɵɦ ɭɱɚɫɬɤɨɦ ɢɧɬɢɦɵ. ɋɬɪɟɥɤɚɦɢ ɭɤɚɡɚɧɵ ɩɹɬɧɚ, ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟ ɫ ɩɨɦɨɳɶɸ MALDI-TOF
ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɢ. Ɉɤɪɚɫɤɚ ɫɟɪɟɛɪɨɦ
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4. ɈȻɋɍɀȾȿɇɂȿ ɊȿɁɍɅɖɌȺɌɈȼ
4.1. Ɋɟɚɤɰɢɹ ɨɫɬɟɨɛɥɚɫɬɨɜ ɧɚ ɉɌȽ
Ɉɞɧɚ ɢɡ ɡɚɞɚɱ ɧɚɲɟɝɨ ɢɫɫɥɟɞɨɜɚɧɢɹ – ɫɨɡɞɚɧɢɟ ɛɚɡɨɜɨɣ, ɷɬɚɥɨɧɧɨɣ ɦɨɞɟɥɢ ɞɥɹ ɨɰɟɧɤɢ ɪɚɡɥɢɱɧɵɯ ɦɚɧɢɩɭɥɹɰɢɣ ɫ ȽɋɄ ɫ ɩɪɢɦɟɧɟɧɢɟɦ
ɦɟɬɨɞɨɥɨɝɢɢ ɩɪɨɬɟɨɦɢɤɢ. ɇɚ ɧɚɱɚɥɶɧɨɦ ɷɬɚɩɟ ɪɚɛɨɬɵ ɛɵɥɢ ɢɫɩɨɥɶɡɨɜɚɧɵ ɨɫɬɟɨɛɥɚɫɬɵ ɞɥɹ ɪɚɡɜɢɬɢɹ ɦɟɬɨɞɚ ɢ ɩɪɨɜɟɪɤɢ ɧɟɤɨɬɨɪɵɯ ɝɢɩɨɬɟɡ,
ɚ ɬɚɤɠɟ ɤɨɧɬɪɨɥɹ ɫɬɢɦɭɥɢɪɨɜɚɧɢɹ ɤɥɟɬɨɤ ɡɚ ɫɱɟɬ ɜɧɟɲɧɢɯ ɮɚɤɬɨɪɨɜ.
ɗɬɨ ɹɜɥɹɟɬɫɹ ɩɟɪɟɯɨɞɧɵɦ ɷɬɚɩɨɦ ɤ ɢɫɫɥɟɞɨɜɚɧɢɸ ɮɚɤɬɨɪɨɜ, ɪɟɝɭɥɢɪɭɸɳɢɯ ȽɋɄ, ɜ ɬɨɦ ɱɢɫɥɟ ɤ ɩɨɧɢɦɚɧɢɸ ɩɪɢɪɨɞɵ ɢɯ ɟɫɬɟɫɬɜɟɧɧɨɝɨ
ɫɨɫɬɨɹɧɢɹ.
ɗɤɫɩɟɪɢɦɟɧɬ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɉɌȽ ɩɪɨɞɟɦɨɧɫɬɪɢɪɨɜɚɥ, ɱɬɨ 2D –
ɷɮɮɟɤɬɢɜɧɵɣ ɢɧɫɬɪɭɦɟɧɬ ɞɥɹ ɧɟɪɚɡɪɭɲɚɸɳɟɝɨ ɦɨɧɢɬɨɪɢɧɝɚ ɢɡɦɟɧɟɧɢɣ ɛɟɥɤɨɜ ɜ ɨɬɜɟɬ ɧɚ ɝɨɪɦɨɧɚɥɶɧɭɸ ɫɬɢɦɭɥɹɰɢɸ.
ɂɡ ɩɪɟɞɜɚɪɢɬɟɥɶɧɵɯ ɪɟɡɭɥɶɬɚɬɨɜ ɜɢɞɧɨ, ɱɬɨ ɉɌȽ (1-34) ɫɬɢɦɭɥɢɪɭɟɬ ɜɵɠɢɜɚɧɢɟ ɧɚɯɨɞɹɳɢɯɫɹ ɜ ɫɬɚɞɢɢ ɩɨɤɨɹ (ɥɢɲɟɧɧɵɯ ɩɢɬɚɧɢɹ) ɨɫɬɟɨɛɥɚɫɬɨɜ. ɂɯ ɨɬɦɢɪɚɧɢɟ, ɚɫɫɨɰɢɢɪɨɜɚɧɧɨɟ ɫ ɮɚɤɬɨɪɨɦ ɬɪɚɧɫɤɪɢɩɰɢɢ 1,
ɫɧɢɠɚɟɬɫɹ ɜ 4 ɪɚɡɚ ɩɨɫɥɟ ɨɛɪɚɛɨɬɤɢ ɉɌȽ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɤɨɧɬɪɨɥɟɦ.
ȼ ɥɢɬɟɪɚɬɭɪɟ ɢɦɟɸɬɫɹ ɫɨɨɛɳɟɧɢɹ ɨ ɩɪɹɦɨɦ ɜɥɢɹɧɢɢ ɨɫɬɟɨɛɥɚɫɬɩɨɞɨɛɧɵɯ ɤɥɟɬɨɱɧɵɯ ɥɢɧɢɣ ɧɚ ɝɟɦɚɬɨɩɨɷɡ in vitro. Ɋɹɞ ɚɜɬɨɪɨɜ ɩɨɥɚɝɚɟɬ, ɱɬɨ ɤɥɟɬɨɱɧɵɟ ɥɢɧɢɢ ɨɫɬɟɨɫɚɪɤɨɦɵ ɧɟ ɩɨɞɞɟɪɠɢɜɚɸɬ ɤɚɤ ɩɪɨɝɟɧɢɬɨɪɧɭɸ ɚɤɬɢɜɧɨɫɬɶ in vitro, ɬɚɤ ɢ ɩɟɪɜɢɱɧɵɟ (primary) ɫɬɜɨɥɨɜɵɟ
ɤɥɟɬɤɢ [14,15].
ɉɪɟɞɩɨɥɚɝɚɟɬɫɹ, ɱɬɨ ɤɥɟɬɨɱɧɵɟ ɥɢɧɢɢ ɨɫɬɟɨɫɚɪɤɨɦɵ ɱɟɥɨɜɟɤɚ ɧɟ
ɫɩɨɫɨɛɧɵ ɩɨɞɞɟɪɠɢɜɚɬɶ ɜɵɠɢɜɚɧɢɟ CD34+ ɤɥɟɬɨɤ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɢɡɡɚ ɜɵɫɨɤɨɝɨ ɫɨɞɟɪɠɚɧɢɹ ɬɪɚɧɫɮɨɪɦɢɪɭɸɳɟɝɨ ɮɚɤɬɨɪɚ ɪɨɫɬɚ (TGF),
ɩɪɨɢɡɜɨɞɢɦɨɝɨ ɤɥɟɬɤɚɦɢ ɷɬɢɯ ɥɢɧɢɣ [85]. ɉɪɢ ɢɫɩɨɥɶɡɨɜɚɧɢɢ ɤɥɟɬɨɱɧɨɣ ɥɢɧɢɢ CAL72 ɨɫɬɟɨɫɚɪɤɨɦɵ ɩɨɤɚɡɚɧɨ, ɱɬɨ ɨɝɪɚɧɢɱɟɧɧɨɟ ɪɚɡɦɧɨ-
89
ɠɟɧɢɟ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɩɪɨɝɟɧɢɬɨɪɧɵɯ ɤɥɟɬɨɤ, ɚɧɚɥɨɝɢɱɧɵɯ ɩɟɪɜɢɱɧɵɦ ɨɫɬɟɨɛɥɚɫɬɚɦ ɱɟɥɨɜɟɤɚ, ɜɩɨɥɧɟ ɜɨɡɦɨɠɧɨ [71].
Ɉɞɧɚɤɨ ɜ ɷɬɢɯ ɨɩɵɬɚɯ ɛɵɥɢ ɢɫɩɨɥɶɡɨɜɚɧɵ CD34+ ɤɥɟɬɤɢ ɢɡ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ, ɱɬɨ ɡɚɬɪɭɞɧɹɟɬ ɢɧɬɟɪɩɪɟɬɚɰɢɸ ɩɨɜɟɞɟɧɢɹ ɨɫɬɟɨɛɥɚɫɬɨɜ
ɩɨ ɨɬɧɨɲɟɧɢɸ ɤ ɤɥɟɬɤɚɦ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ [71]. Ɉɬɦɟɬɢɦ ɬɚɤɠɟ, ɱɬɨ ɨɫɬɟɨɫɚɪɤɨɦɚ ɤɥɟɬɨɱɧɨɣ ɥɢɧɢɢ U2-OS ɩɨɞɞɟɪɠɢɜɚɟɬ ɩɪɨɥɢɮɟɪɚɰɢɸ
ɪɚɧɧɢɯ ɤɥɟɬɨɤ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ [73]. ȼɡɹɬɵɟ ɜɦɟɫɬɟ, ɷɬɢ ɢɫɫɥɟɞɨɜɚɧɢɹ
ɭɤɚɡɵɜɚɸɬ ɧɚ ɬɨ, ɱɬɨ, ɯɨɬɹ ɨɫɬɟɨɫɚɪɤɨɦɚ ɢ ɬɪɚɧɫɮɨɪɦɢɪɨɜɚɧɧɵɟ ɤɥɟɬɨɱɧɵɟ ɥɢɧɢɢ ɨɫɬɟɨɛɥɚɫɬɨɜ ɦɨɝɭɬ ɩɨɞɞɟɪɠɢɜɚɬɶ ɩɪɨɥɢɮɟɪɚɰɢɸ, ɢɯ
ɫɩɨɫɨɛɧɨɫɬɶ ɩɨɞɞɟɪɠɢɜɚɬɶ ɪɚɧɧɢɟ ȽɋɄ ɯɨɬɶ ɢ ɜɨɡɦɨɠɧɚ, ɧɨ ɜɟɫɶɦɚ
ɨɝɪɚɧɢɱɟɧɧɚ.
ɋɬɜɨɥɨɜɨɫɬɶ – ɤɥɸɱɟɜɨɟ ɫɜɨɣɫɬɜɨ ɜɫɟɯ ɋɄ. Ɍɚɤ ɩɪɢɧɹɬɨ ɧɚɡɵɜɚɬɶ
ɢɯ ɫɩɨɫɨɛɧɨɫɬɶ ɤ ɫɚɦɨɨɛɧɨɜɥɟɧɢɸ ɢ ɜɨɡɦɨɠɧɨɫɬɶ ɫɨɡɞɚɜɚɬɶ ɞɢɮɮɟɪɟɧɰɢɪɭɸɳɟɟɫɹ ɩɨɬɨɦɫɬɜɨ. Ʉɚɤɢɟ ɮɚɤɬɨɪɵ ɭɩɪɚɜɥɹɸɬ ɷɬɨɣ ɫɩɨɫɨɛɧɨɫɬɶɸ?
Ɉɞɧɚ ɢɡ ɝɢɩɨɬɟɡ, ɨɬɜɟɱɚɸɳɢɯ ɧɚ ɷɬɨɬ ɜɨɩɪɨɫ, ɭɤɚɡɵɜɚɟɬ ɧɚ ɪɨɥɶ ɦɢɤɪɨɨɤɪɭɠɟɧɢɹ ɋɄ [9, 84,107], ɩɨɥɭɱɢɜɲɟɝɨ ɧɚɡɜɚɧɢɟ ɧɢɲɢ ɋɄ. ȼ ɷɬɨɣ
ɫɜɹɡɢ ɜ ɧɚɲɟɣ ɪɚɛɨɬɟ ɢɫɩɨɥɶɡɨɜɚɧɵ ɨɫɬɟɨɛɥɚɫɬɵ, ɹɜɥɹɸɳɢɟɫɹ ɜɚɠɧɵɦɢ ɤɨɦɩɨɧɟɧɬɚɦɢ ɧɢɲɢ. Ɉɫɬɟɨɛɥɚɫɬɵ ɨɬɧɨɫɢɬɟɥɶɧɨ ɩɪɨɫɬɨ ɝɨɬɨɜɹɬɫɹ ɞɥɹ ɢɫɫɥɟɞɨɜɚɬɟɥɶɫɤɢɯ ɰɟɥɟɣ ɢ ɦɨɝɭɬ ɩɨɫɥɭɠɢɬɶ ɦɚɬɟɪɢɚɥɨɦ
ɞɥɹ ɫɨɡɞɚɧɢɹ ɩɪɨɬɨɤɨɥɚ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ. Ɉɫɬɟɨɛɥɚɫɬɵ ɞɚɸɬ ɜɨɡɦɨɠɧɨɫɬɶ ɢɡɭɱɟɧɢɹ ɫɬɢɦɭɥɢɪɨɜɚɧɢɹ ɤɥɟɬɨɤ ɡɚ ɫɱɟɬ ɜɧɟɲɧɢɯ ɮɚɤɬɨɪɨɜ, ɚ
ɨɩɵɬɵ ɫ ɧɢɦɢ ɹɜɥɹɸɬɫɹ ɩɟɪɟɯɨɞɧɵɦ ɷɬɚɩɨɦ ɤ ɢɫɫɥɟɞɨɜɚɧɢɸ ɮɚɤɬɨɪɨɜ,
ɪɟɝɭɥɢɪɭɸɳɢɯ ȽɋɄ.
ɇɚɩɪɢɦɟɪ, ɦɨɠɧɨ ɨɠɢɞɚɬɶ, ɱɬɨ Jagged1 (Jag1), ɜɵɞɟɥɹɟɦɵɣ ɨɫɬɟɨɛɥɚɫɬɚɦɢ ɜ ɨɬɜɟɬ ɧɚ ɨɛɪɚɛɨɬɤɭ ɉɌȽ, ɜɥɢɹɟɬ ɧɚ ȽɋɄ ɩɨ ɫɢɝɧɚɥɶɧɨɦɭ ɩɭɬɢ
ɱɟɪɟɡ ɪɟɰɟɩɬɨɪ Notch-1 [28, 73]. ɉɨɢɫɤ ɮɚɤɬɨɪɨɜ, ɤɨɬɨɪɵɟ ɫɩɨɫɨɛɫɬɜɭɸɬ
ɪɚɡɦɧɨɠɟɧɢɸ ȽɋɄ ɜ ɤɭɥɶɬɭɪɟ, ɩɪɨɜɨɞɢɥɫɹ ɢ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɨɝɨ Jag1 [96]. ɉɪɢ ɷɬɨɦ Jag1-ɫɮɟɪɵ ɢɦɢɬɢɪɨɜɚɥɢ ɞɟɣɫɬɜɢɟ ɨɫ90
ɬɟɨɛɥɚɫɬɨɜ ɜ ɧɢɲɟ ȽɋɄ. Ɉɩɪɟɞɟɥɢɜ ɧɢɲɭ ɤɚɤ ɞɟɬɟɪɦɢɧɚɧɬɭ ɜ ɪɟɝɭɥɹɰɢɢ
ȽɋɄ, ɪɨɥɶ ɜɧɭɬɪɟɧɧɢɯ ɫɢɝɧɚɥɨɜ ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ ɫ ɧɨɜɨɣ ɬɨɱɤɢ ɡɪɟɧɢɹ –
ɧɟ ɬɨɥɶɤɨ ɤɚɤ ɪɟɝɭɥɢɪɭɸɳɢɯ ɫɚɦɢ ɩɨ ɫɟɛɟ, ɧɨ ɢ ɜɨ ɜɡɚɢɦɨɞɟɣɫɬɜɢɢ ɫ
ɞɪɭɝɢɦɢ ɢɧɫɬɪɭɦɟɧɬɚɦɢ (ɧɚɩɪɢɦɟɪ, ɰɢɬɨɤɢɧɚɦɢ) ɞɥɹ ɤɨɥɥɟɤɬɢɜɧɨɝɨ
ɜɥɢɹɧɢɹ ɧɢɲɢ ɧɚ ɮɭɧɤɰɢɨɧɢɪɨɜɚɧɢɟ ɋɄ.
ɉɪɟɞɩɨɥɚɝɚɟɦɵɟ ɷɮɮɟɤɬɵ ɦɢɤɪɨɫɮɟɪ ɫ Jag1 ɢ ɢɯ ɚɧɚɥɨɝɨɜ in vivo ɜ
ɮɨɪɦɟ ɨɫɬɟɨɛɥɚɫɬɨɜ ɧɚ ȽɋɄ ɹɜɥɹɸɬɫɹ ɬɨɣ ɫɬɚɪɬɨɜɨɣ ɬɨɱɤɨɣ, ɢɫɯɨɞɹ ɢɡ
ɤɨɬɨɪɨɣ ɩɪɨɬɟɨɦɢɤɚ ɞɚɟɬ ɜɨɡɦɨɠɧɨɫɬɶ ɢɫɫɥɟɞɨɜɚɬɶ ɪɨɥɶ ɨɫɬɟɨɛɥɚɫɬɨɜ ɜ ɩɪɨɥɢɮɟɪɚɰɢɢ ȽɋɄ.
Ʉɪɨɦɟ ɬɨɝɨ, ɧɚɦɢ ɞɨɫɬɢɝɧɭɬɚ ɨɩɬɢɦɢɡɚɰɢɹ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɞɨɫɬɭɩɧɵɯ ɬɟɯɧɨɥɨɝɢɣ, ɤɨɦɛɢɧɢɪɨɜɚɧɢɟ ɤɨɬɨɪɵɯ ɩɨɡɜɨɥɢɥɨ ɩɨɥɭɱɢɬɶ
ɭɥɭɱɲɟɧɧɵɟ ɪɟɡɭɥɶɬɚɬɵ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ. Ƚɥɚɜɧɨɣ ɨɫɨɛɟɧɧɨɫɬɶɸ ɩɪɟɞɥɚɝɚɟɦɨɝɨ ɦɟɬɨɞɢɱɟɫɤɨɝɨ ɩɨɞɯɨɞɚ ɹɜɥɹɟɬɫɹ ɬɪɟɯɫɬɭɩɟɧɱɚɬɚɹ ɩɪɨɰɟɞɭɪɚ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɹ ɛɢɨɥɨɝɢɱɟɫɤɨɝɨ ɦɚɬɟɪɢɚɥɚ, ɜɟɞɭɳɚɹ ɤ ɩɨɜɵɲɟɧɢɸ ɷɮɮɟɤɬɢɜɧɨɫɬɢ ɪɚɡɞɟɥɟɧɢɹ ɛɟɥɤɨɜ ɦɟɬɨɞɨɦ ɞɜɭɦɟɪɧɨɝɨ ɝɟɥɶ-ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɧɚ ɩɨɥɢɚɤɪɢɥɚɦɢɞɟ.
Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɦɵ ɚɤɰɟɧɬɢɪɭɟɦ ɜɧɢɦɚɧɢɟ ɧɚ ɜɚɠɧɨɫɬɢ ɩɨɞɝɨɬɨɜɤɢ ɨɛɪɚɡɰɚ (ɤɥɟɬɨɱɧɨɝɨ ɫɨɞɟɪɠɢɦɨɝɨ), ɜɤɥɸɱɚɹ ɭɥɶɬɪɚɡɜɭɤɨɜɨɟ
ɪɚɡɪɭɲɟɧɢɟ ɦɟɦɛɪɚɧ ɢ ɪɚɡɞɟɥɟɧɢɟ ɫɭɛɤɥɟɬɨɱɧɵɯ ɱɚɫɬɢɰ, ɩɨɡɜɨɥɹɸɳɟɟ ɜ ɞɚɥɶɧɟɣɲɟɦ ɩɪɨɜɨɞɢɬɶ ɚɧɚɥɢɡ ɛɟɥɤɨɜ, ɩɪɢɫɭɬɫɬɜɭɸɳɢɯ
ɜ ɧɢɡɤɢɯ ɤɨɧɰɟɧɬɪɚɰɢɹɯ. ȼ ɱɚɫɬɧɨɫɬɢ, ɞɢɮɮɟɪɟɧɰɢɚɥɶɧɨɟ ɷɤɫɬɪɚɝɢɪɨɜɚɧɢɟ ɛɟɥɤɨɜ ɨɫɭɳɟɫɬɜɥɹɟɬɫɹ ɫ ɩɨɦɨɳɶɸ ɤɨɦɦɟɪɱɟɫɤɢ ɞɨɫɬɭɩɧɨɝɨ ɧɚɛɨɪɚ ɪɟɚɝɟɧɬɨɜ ProteoExtract® Subcellular Proteome Extraction Kit (S-PEK, Calbiochem, Germany). ɗɬɨɬ ɧɚɛɨɪ ɫɨɞɟɪɠɢɬ
ɷɤɫɬɪɚɤɰɢɨɧɧɵɟ ɛɭɮɟɪɧɵɟ ɪɚɫɬɜɨɪɵ, ɩɪɢɝɨɬɨɜɥɟɧɧɵɟ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ ɫɨɟɞɢɧɟɧɢɣ ɜɵɫɨɤɨɣ ɱɢɫɬɨɬɵ, ɫɦɟɫɶ ɩɪɨɬɟɚɡ ɢ ɧɭɤɥɟɚɡɭ,
ɭɫɬɪɚɧɹɸɳɭɸ ɧɭɤɥɟɢɧɨɜɵɟ ɤɢɫɥɨɬɵ. Ɉɞɧɢɦ ɢɡ ɩɪɟɢɦɭɳɟɫɬɜ SPEK ɹɜɥɹɟɬɫɹ ɜɨɡɦɨɠɧɨɫɬɶ ɢɡɛɢɪɚɬɟɥɶɧɨɝɨ ɢ ɦɹɝɤɨɝɨ ɷɤɫɬɪɚɝɢɪɨ91
ɜɚɧɢɹ ɤɨɦɩɨɧɟɧɬɨɜ ɫɭɛɤɥɟɬɨɱɧɵɯ ɫɬɪɭɤɬɭɪ ɫɩɟɰɢɚɥɶɧɵɦɢ ɫɦɟɫɹɦɢ
ɪɟɚɝɟɧɬɨɜ. Ȼɥɚɝɨɞɚɪɹ ɷɬɨɦɭ, ɰɟɥɵɣ ɩɪɨɬɟɨɦ ɩɪɟɜɪɚɳɚɟɬɫɹ ɜ ɫɭɛɩɪɨɬɟɨɦɵ ɦɟɧɶɲɟɣ ɫɥɨɠɧɨɫɬɢ ɜ ɨɬɧɨɲɟɧɢɢ ɫɜɨɟɝɨ ɫɨɫɬɚɜɚ. ɉɨɷɬɚɩɧɨɟ ɩɪɢɦɟɧɟɧɢɟ ɬɪɟɯ ɛɭɮɟɪɧɵɯ ɫɦɟɫɟɣ ɩɨɡɜɨɥɹɟɬ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨ ɜɵɞɟɥɢɬɶ ɬɪɢ ɮɪɚɤɰɢɢ ɛɟɥɤɨɜ ɫ ɪɚɫɬɜɨɪɢɦɨɫɬɶɸ, ɢɡɦɟɧɹɸɳɟɣɫɹ ɨɬ ɦɚɤɫɢɦɚɥɶɧɨɣ ɤ ɦɢɧɢɦɚɥɶɧɨɣ. ɇɚ ɫɥɟɞɭɸɳɟɣ ɫɬɚɞɢɢ ɪɚɛɨɬɵ ɩɪɢɦɟɧɹɟɬɫɹ ɧɚɛɨɪ ɪɟɚɝɟɧɬɨɜ 2D Clean-Up Kit (Amersham Biosciences), ɡɚɜɟɪɲɚɸɳɢɣ ɢ ɨɩɬɢɦɢɡɢɪɭɸɳɢɣ ɩɨɞɝɨɬɨɜɤɭ ɨɛɪɚɡɰɨɜ
ɤ ɞɜɭɦɟɪɧɨɦɭ ɝɟɥɶ-ɷɥɟɤɬɪɨɮɨɪɟɡɭ. ɗɬɢ ɪɟɚɝɟɧɬɵ ɤɨɥɢɱɟɫɬɜɟɧɧɨ
ɨɫɚɠɞɚɸɬ ɛɟɥɤɢ, ɨɫɬɚɜɥɹɹ ɩɨɦɟɯɨɨɛɪɚɡɭɸɳɢɟ ɫɨɟɞɢɧɟɧɢɹ ɜ ɪɚɫɬɜɨɪɟɧɧɨɦ ɫɨɫɬɨɹɧɢɢ.
ɋɩɨɫɨɛɧɨɫɬɶ ɉɌȽ ɫɬɢɦɭɥɢɪɨɜɚɬɶ ɩɪɨɥɢɮɟɪɚɰɢɸ ɪɚɧɧɢɯ ɤɪɨɜɟɬɜɨɪɧɵɯ ɩɪɟɞɲɟɫɬɜɟɧɧɢɤɨɜ, ɜɟɪɨɹɬɧɨ, ɦɨɠɧɨ ɢɫɩɨɥɶɡɨɜɚɬɶ ɞɥɹ ɷɤɫɩɚɧɫɢɢ ȽɋɄ [2]. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɧɚɦɢ ɧɟ ɬɨɥɶɤɨ ɩɨɥɭɱɟɧɵ ɞɚɧɧɵɟ
ɩɨ ɩɪɨɬɟɨɦɧɨɦɭ ɩɪɨɮɢɥɸ ɨɫɬɟɨɛɥɚɫɬɨɜ, ɧɨ ɢ ɫɞɟɥɚɧ ɨɱɟɪɟɞɧɨɣ ɲɚɝ
ɤ ɢɡɭɱɟɧɢɸ ɜɨɡɦɨɠɧɨɫɬɢ ɜɨɡɞɟɣɫɬɜɢɹ ɧɚ ɤɪɨɜɟɬɜɨɪɧɵɟ «ɧɢɲɢ» ɢɥɢ ɧɚ
ɦɨɥɟɤɭɥɵ ɫɢɝɧɚɥɶɧɵɯ ɩɭɬɟɣ ɜɡɚɢɦɨɞɟɣɫɬɜɢɹ ȽɋɄ ɫ ɦɢɤɪɨɨɤɪɭɠɟɧɢɟɦ
ɞɥɹ ɫɬɢɦɭɥɹɰɢɢ ɢɯ ɪɨɫɬɚ.
4.2 ɏɚɪɚɤɬɟɪɢɫɬɢɤɚ ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ
4.2.1 Ȼɟɥɤɨɜɵɣ ɩɪɨɮɢɥɶ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɤɥɟɬɨɤ
ɇɟɫɦɨɬɪɹ ɧɚ ɩɪɨɢɫɯɨɠɞɟɧɢɟ ɨɛɪɚɡɰɨɜ ɆɇɄ ɢɡ ɨɞɧɨɣ ɚɥɢɤɜɨɬɵ
ɉɄ, ɛɟɥɤɨɜɵɟ ɩɪɨɮɢɥɢ ɨɛɪɚɡɰɨɜ Ⱥ ɢ Ȼ ɨɛɧɚɪɭɠɢɥɢ ɧɟɛɨɥɶɲɢɟ ɨɬɥɢɱɢɹ. Ɉɛɪɚɡɰɵ ɯɪɚɧɢɥɢɫɶ ɜ ɫɯɨɞɧɵɯ ɭɫɥɨɜɢɹɯ, ɚ ɪɚɫɯɨɠɞɟɧɢɹ ɜ
ɞɚɧɧɵɯ, ɤɚɤ ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ, ɨɛɭɫɥɨɜɥɟɧɵ ɪɚɡɥɢɱɧɵɦɢ ɜɧɟɲɧɢɦɢ
ɮɚɤɬɨɪɚɦɢ ɷɤɫɩɟɪɢɦɟɧɬɚ. ɇɚɩɪɢɦɟɪ, ɢɫɬɨɱɧɢɤɚɦɢ ɬɚɤɢɯ ɪɚɫɯɨɠɞɟ-
92
ɧɢɣ ɦɨɝɭɬ ɛɵɬɶ ɩɨɥɢɚɤɪɢɥɚɦɢɞɧɵɟ ɝɟɥɢ, ɢɫɩɨɥɶɡɭɟɦɵɟ ɞɥɹ ɷɤɫɩɟɪɢɦɟɧɬɨɜ.
Ɉɛɚ ɧɚɩɪɚɜɥɟɧɢɹ ɪɚɡɞɟɥɟɧɢɹ ɫ ɩɨɦɨɳɶɸ ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɩɪɟɞɩɨɥɚɝɚɸɬ ɢɫɩɨɥɶɡɨɜɚɧɢɟ ɪɚɡɧɵɯ ɝɟɥɟɣ ɞɥɹ ɤɚɠɞɨɝɨ ɨɛɪɚɡɰɚ, ɩɨɷɬɨɦɭ
ɪɚɡɥɢɱɢɹ ɜ ɝɟɥɹɯ ɦɨɝɭɬ ɩɪɢɜɟɫɬɢ ɤ ɪɚɫɯɨɠɞɟɧɢɹɦ ɜ ɪɟɡɭɥɶɬɚɬɚɯ. Ⱦɥɹ
ɦɢɧɢɦɢɡɚɰɢɢ ɷɬɨɝɨ ɜɥɢɹɧɢɹ ɦɨɠɧɨ ɢɫɩɨɥɶɡɨɜɚɬɶ ɩɪɟɞɜɚɪɢɬɟɥɶɧɨ
ɨɬɨɛɪɚɧɧɵɟ ɝɟɥɢ ɩɨɜɵɲɟɧɧɨɣ ɫɬɚɛɢɥɶɧɨɫɬɢ, ɫ ɜɨɫɩɪɨɢɡɜɨɞɢɦɨɫɬɶɸ,
ɡɚɜɢɫɹɳɟɣ ɨɬ ɨɛɨɪɭɞɨɜɚɧɢɹ, ɩɪɢɦɟɧɹɟɦɨɝɨ ɩɪɨɢɡɜɨɞɢɬɟɥɟɦ. ȼ ɩɟɪɜɨɟ
ɧɚɩɪɚɜɥɟɧɢɟ ɪɚɡɞɟɥɟɧɢɹ ɜɨɜɥɟɱɟɧɵ IPG-ɫɬɪɢɩɵ, ɤɨɬɨɪɵɟ ɢɦɟɸɬ ɨɫɚɞɨɱɧɵɣ ɝɪɚɞɢɟɧɬ ɪɇ (3-11 ɜ ɧɚɲɟɦ ɫɥɭɱɚɟ). ȼɚɪɢɚɰɢɢ ɜ ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɵɯ ɷɥɟɤɬɪɨɥɢɬɚɯ, ɢɫɩɨɥɶɡɭɟɦɵɯ ɞɥɹ ɫɨɡɞɚɧɢɹ ɝɪɚɞɢɟɧɬɚ, ɩɪɢɜɨɞɹɬ ɤ ɫɦɟɳɟɧɢɸ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɜɞɨɥɶ ɨɫɢ ɏ (ɩɟɪɜɨɟ ɧɚɩɪɚɜɥɟɧɢɟ
ɪɚɡɞɟɥɟɧɢɹ) ɜ ɪɟɡɭɥɶɬɢɪɭɸɳɟɦ ɝɟɥɟ. ȼɨ ɜɬɨɪɨɦ ɧɚɩɪɚɜɥɟɧɢɢ ɪɚɡɞɟɥɟɧɢɹ ɩɥɨɬɧɨɫɬɶ ɝɪɚɞɢɟɧɬɧɨ-ɭɩɚɤɨɜɚɧɧɨɝɨ (4–12%) ɉȺȺȽ ɬɚɤɠɟ ɦɨɠɟɬ
ɩɪɢɜɟɫɬɢ ɤ ɜɚɪɢɚɛɟɥɶɧɨɫɬɢ.
ȼɟɥɢɱɢɧɚ ɩɹɬɧɚ ɦɨɠɟɬ ɧɚɛɥɸɞɚɬɶɫɹ ɢ ɤɚɤ «ɦɨɧɬɚɠɧɵɣ ɨɛɪɚɡ»,
ɩɪɟɞɫɬɚɜɥɹɸɳɢɣ ɫɨɛɨɣ ɬɪɟɯɦɟɪɧɨɟ ɢɡɨɛɪɚɠɟɧɢɟ ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ.
Ɍɪɟɯɦɟɪɧɵɣ ɢɧɫɬɪɭɦɟɧɬ ɜɢɡɭɚɥɢɡɚɰɢɢ («ɦɨɧɬɚɠɧɵɣ ɨɛɪɚɡ») ɩɨɡɜɨɥɹɟɬ
ɩɪɨɜɨɞɢɬɶ ɛɨɥɟɟ ɬɳɚɬɟɥɶɧɨɟ ɢɫɫɥɟɞɨɜɚɧɢɟ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ. Ɍɚɤɨɣ ɩɨɞɯɨɞ ɦɨɠɟɬ ɢɫɩɨɥɶɡɨɜɚɬɶɫɹ ɭɬɨɱɧɟɧɢɹ ɤɚɤɢɯ-ɥɢɛɨ ɫɜɟɞɟɧɢɣ ɢ ɨɛɧɚɪɭɠɟɧɢɹ ɢɡɦɟɧɟɧɢɣ ɜ ɛɟɥɤɨɜɵɯ ɭɪɨɜɧɹɯ. Ʉɨɧɤɪɟɬɧɵɟ ɬɨɱɤɢ ɦɨɝɭɬ
ɛɵɬɶ ɨɬɨɛɪɚɧɵ ɢ ɢɡɭɱɟɧɵ ɛɨɥɟɟ ɩɨɞɪɨɛɧɨ ɞɥɹ ɧɚɛɥɸɞɟɧɢɹ ɢɡɦɟɧɟɧɢɣ ɢɥɢ ɤɨɧɫɬɚɬɚɰɢɢ ɢɯ ɨɬɫɭɬɫɬɜɢɹ. ɗɬɨ ɜɚɠɧɨ ɞɥɹ ɩɨɞɬɜɟɪɠɞɟɧɢɹ
ɭɜɟɪɟɧɧɨɫɬɢ ɜ ɪɟɡɭɥɶɬɚɬɚɯ ɚɜɬɨɦɚɬɢɡɢɪɨɜɚɧɧɨɝɨ ɢ ɤɨɦɩɶɸɬɟɪɧɨɝɨ
ɚɧɚɥɢɡɚ.
Ɉɞɧɢɦ ɢɡ ɨɫɧɨɜɧɵɯ ɬɪɟɛɨɜɚɧɢɣ ɤ ɩɪɨɬɟɨɦɢɤɟ ɤɚɤ ɤ ɢɧɫɬɪɭɦɟɧɬɭ ɞɥɹ ɦɨɧɢɬɨɪɢɧɝɚ ɢɡɦɟɧɟɧɢɣ ɛɟɥɤɚ ɹɜɥɹɟɬɫɹ ɫɩɨɫɨɛɧɨɫɬɶ ɨɛɧɚɪɭɠɢɜɚɬɶ ɷɬɢ ɢɡɦɟɧɟɧɢɹ ɢ ɢɯ ɜɟɥɢɱɢɧɭ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɬɪɟɛɭɟɬɫɹ ɢɫ93
ɤɥɸɱɟɧɢɟ ɢɡ ɪɚɫɫɦɨɬɪɟɧɢɹ ɨɲɢɛɨɱɧɵɯ ɪɟɡɭɥɶɬɚɬɨɜ (ɜ ɮɨɪɦɟ ɡɚɝɪɹɡɧɟɧɢɣ, ɮɨɧɨɜɵɯ ɲɭɦɨɜ, ɩɥɨɯɢɯ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɯ ɩɪɨɰɟɞɭɪ
ɢɥɢ ɩɪɨɫɬɨ ɧɟɞɨɫɬɚɬɨɱɧɨ ɡɧɚɱɢɦɵɯ ɢɡɦɟɧɟɧɢɣ), ɜɥɢɹɸɳɢɯ ɧɚ ɧɚɲɭ
ɫɩɨɫɨɛɧɨɫɬɶ ɜɵɹɜɥɹɬɶ ɧɚɢɛɨɥɟɟ ɡɧɚɱɢɦɵɟ. Ⱥ ɢɦɢ ɹɜɥɹɸɬɫɹ ɢɡɦɟɧɟɧɢɹ ɛɟɥɤɨɜ, ɦɨɞɢɮɢɰɢɪɭɸɳɢɟ ɛɢɨɥɨɝɢɱɟɫɤɭɸ ɚɤɬɢɜɧɨɫɬɶ. ȼ ɷɬɨɣ
ɫɜɹɡɢ ɧɚɦɢ ɩɪɟɞɥɨɠɟɧɵ ɩɨɪɨɝɨɜɵɟ ɡɧɚɱɟɧɢɹ ɜ ɜɢɞɟ ɤɨɷɮɮɢɰɢɟɧɬɚ,
ɨɩɪɟɞɟɥɹɸɳɟɝɨ ɤɪɚɬɧɨɫɬɶ ɭɜɟɥɢɱɟɧɢɹ (ɢɥɢ ɭɦɟɧɶɲɟɧɢɹ) ɪɚɡɦɟɪɚ
ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ.
ɑɭɜɫɬɜɢɬɟɥɶɧɨɫɬɶ ɩɨ ɨɬɧɨɲɟɧɢɸ ɤ ɨɛɧɚɪɭɠɟɧɢɸ ɛɟɥɤɨɜɨɝɨ
ɩɹɬɧɚ ɡɚɜɢɫɢɬ ɨɬ ɬɪɟɯ ɩɚɪɚɦɟɬɪɨɜ: 1) ɷɮɮɟɤɬɢɜɧɨɫɬɢ ɤɪɚɫɢɬɟɥɹ ɞɥɹ
ɨɤɪɚɫɤɢ ɛɟɥɤɚ; 2) ɬɟɯɧɨɥɨɝɢɢ ɫɤɚɧɢɪɨɜɚɧɢɹ ɞɥɹ ɩɨɥɭɱɟɧɢɹ ɢɡɨɛɪɚɠɟɧɢɹ ɝɟɥɹ; 3) ɫɩɨɫɨɛɧɨɫɬɢ ɩɪɨɝɪɚɦɦɧɨɝɨ ɨɛɟɫɩɟɱɟɧɢɹ ɨɬɥɢɱɚɬɶ
ɩɹɬɧɚ ɨɬ ɮɨɧɚ. ɇɨ ɹɫɧɨ, ɱɬɨ ɜɫɟ ɷɬɢ ɮɚɤɬɨɪɵ ɜɧɭɬɪɟɧɧɟ ɨɩɨɫɪɟɞɨɜɚɧɵ ɤɨɥɢɱɟɫɬɜɨɦ ɩɪɢɫɭɬɫɬɜɭɸɳɟɝɨ ɛɟɥɤɚ. ɂɫɯɨɞɹ ɢɡ ɩɪɟɞɩɨɥɨɠɟɧɢɹ,
ɱɬɨ ɩɟɪɜɵɟ ɞɜɚ ɮɚɤɬɨɪɚ ɹɜɥɹɸɬɫɹ ɩɨɫɬɨɹɧɧɵɦɢ ɜ ɪɚɦɤɚɯ ɨɞɧɨɝɨ
ɷɤɫɩɟɪɢɦɟɧɬɚ, ɬɚɤ ɤɚɤ ɨɧɢ ɧɟ ɫɜɹɡɚɧɵ ɫ ɨɛɪɚɡɰɚɦɢ, ɩɪɨɝɪɚɦɦɧɨɟ
ɨɛɟɫɩɟɱɟɧɢɟ – ɟɞɢɧɫɬɜɟɧɧɵɣ ɢɫɬɨɱɧɢɤ ɨɝɪɚɧɢɱɟɧɢɣ ɩɪɢ ɨɛɧɚɪɭɠɟɧɢɢ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ. Ɉɞɧɚɤɨ ɨɧɨ ɱɭɜɫɬɜɢɬɟɥɶɧɨ ɤ ɜɚɪɢɚɛɟɥɶɧɨɫɬɢ
ɦɟɠɞɭ ɨɛɪɚɡɰɚɦɢ. ȼ ɱɚɫɬɧɨɫɬɢ, ɩɪɨɝɪɚɦɦɚ ɨɫɭɳɟɫɬɜɥɹɟɬ ɜɵɱɢɬɚɧɢɟ
ɮɨɧɚ ɞɥɹ ɜɵɞɟɥɟɧɢɹ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɢ ɨɰɟɧɤɢ ɢɯ ɜɟɥɢɱɢɧɵ. ɗɬɚ
ɫɩɨɫɨɛɧɨɫɬɶ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɬɶ ɩɹɬɧɚ ɨɩɪɟɞɟɥɟɧɚ ɤɚɤ ɧɢɠɧɢɣ ɩɪɟɞɟɥ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ (ɪɢɫ. 4.1ɛ).
ȼɟɪɯɧɢɣ ɩɪɟɞɟɥ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ (ɪɢɫ. 4.1ɚ) ɨɩɪɟɞɟɥɹɟɬɫɹ ɤɚɤ
ɫɩɨɫɨɛɧɨɫɬɶ ɩɪɨɝɪɚɦɦɵ ɭɫɬɚɧɨɜɢɬɶ ɦɚɤɫɢɦɚɥɶɧɭɸ ɤɨɧɰɟɧɬɪɚɰɢɸ
ɤɨɧɤɪɟɬɧɨɝɨ ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ. ɉɨ ɫɭɬɢ, ɷɬɨɬ ɩɪɟɞɟɥ ɹɜɥɹɟɬɫɹ ɦɚɤɫɢɦɚɥɶɧɨɣ ɢɧɬɟɧɫɢɜɧɨɫɬɶɸ ɛɟɥɤɨɜɨɝɨ ɩɹɬɧɚ, ɜɵɲɟ ɤɨɬɨɪɨɣ ɢɧɬɟɧɫɢɜɧɨɫɬɢ ɧɟ ɪɟɝɢɫɬɪɢɪɭɟɬɫɹ. ȼ ɛɨɥɟɟ ɩɪɨɫɬɨɣ ɬɟɪɦɢɧɨɥɨɝɢɢ, ɷɬɨ ɫɚɦɚɹ
ɬɟɦɧɚɹ ɬɨɱɤɚ ɩɹɬɧɚ ɧɚ ɝɟɥɟ, ɤɨɬɨɪɚɹ ɧɟ ɦɨɠɟɬ ɛɵɬɶ ɢɡɦɟɪɟɧɚ ɤɚɤ
94
ɩɪɨɰɟɧɬ ɫɟɪɵɯ ɩɹɬɟɧ ɦɟɠɞɭ ɫɚɦɨɣ ɜɵɫɨɤɨɣ ɢ ɫɚɦɨɣ ɧɢɡɤɨɣ ɢɧɬɟɧɫɢɜɧɨɫɬɶɸ. ɋɚɦɚɹ ɬɟɦɧɚɹ ɬɨɱɤɚ ɧɟ ɦɨɠɟɬ ɛɵɬɶ ɨɩɢɫɚɧɚ ɜɟɥɢɱɢɧɨɣ,
ɫɜɹɡɚɧɧɨɣ ɫ ɞɪɭɝɢɦɢ ɢɧɬɟɧɫɢɜɧɨɫɬɹɦɢ ɩɢɤɨɜ. ɗɬɨ ɢɦɟɧɧɨ ɬɚ ɬɨɱɤɚ,
ɤɨɝɞɚ ɞɨɫɬɢɝɚɟɬɫɹ ɜɟɪɯɧɢɣ ɩɪɟɞɟɥ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ. ȼɟɪɯɧɢɣ ɩɪɟɞɟɥ ɨɩɪɟɞɟɥɹɟɬɫɹ ɤɨɦɩɶɸɬɟɪɧɵɦ ɪɟɲɟɧɢɟɦ ɢ ɬɟɯɧɨɥɨɝɢɣ ɨɤɪɚɲɢɜɚɧɢɹ. Ⱦɢɧɚɦɢɱɟɫɤɢɣ ɩɨɤɚɡɚɬɟɥɶ-ɢɧɬɟɪɜɚɥ («range of») 2,5×103 ɨɡɧɚɱɚɟɬ,
ɱɬɨ ɭɜɟɥɢɱɟɧɢɟ ɢɧɬɟɧɫɢɜɧɨɫɬɢ ɩɢɤɚ ɫɨɫɬɚɜɥɹɟɬ 2,5×103 ɪɚɡ, ɱɬɨ ɢ ɧɚɛɥɸɞɚɟɬɫɹ ɞɥɹ 1-ɣ ɮɪɚɤɰɢɢ ɨɛɪɚɡɰɚ ɆɇɄ (ɪɢɫ. 4.1).
ɚ
ɛ
Ɋɢɫ. 4.1. ȼɟɪɯɧɢɣ (ɚ) ɢ ɧɢɠɧɢɣ (ɛ) ɩɪɟɞɟɥɵ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ ɩɪɢ ɨɛɧɚɪɭɠɟɧɢɢ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ
ɉɪɟɞɟɥɵ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ ɫɢɥɶɧɨ ɡɚɜɢɫɹɬ ɨɬ ɤɨɥɢɱɟɫɬɜɚ ɧɚɧɟɫɟɧɧɨɝɨ ɛɟɥɤɚ. ɑɟɦ ɛɨɥɶɲɟ ɛɟɥɤɚ ɧɚɧɟɫɟɧɨ ɧɚ ɝɟɥɶ, ɬɟɦ ɛɨɥɟɟ ɜɟɪɨɹɬɧɨ, ɱɬɨ ɩɨɥɭɱɟɧɧɵɟ ɛɟɥɤɨɜɵɟ ɩɹɬɧɚ ɞɨɫɬɢɝɧɭɬ ɫɜɨɟɝɨ ɜɟɪɯɧɟɝɨ ɩɪɟɞɟɥɚ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ. ɇɚɧɟɫɟɧɢɟ ɧɚ ɝɟɥɶ ɧɟɞɨɫɬɚɬɨɱɧɨɝɨ ɤɨɥɢɱɟɫɬɜɚ
ɛɟɥɤɚ ɩɪɢɜɨɞɢɬ ɤ ɩɨɥɭɱɟɧɢɸ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ, ɞɨɫɬɢɝɚɸɳɢɯ ɫɜɨɟɝɨ
ɧɢɠɧɟɝɨ ɩɪɟɞɟɥɚ ɱɭɜɫɬɜɢɬɟɥɶɧɨɫɬɢ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɨɱɟɧɶ ɜɚɠɧɨ ɧɚɧɨɫɢɬɶ ɧɚ ɝɟɥɶ ɬɚɤɢɟ ɤɨɥɢɱɟɫɬɜɚ ɛɟɥɤɚ, ɱɬɨɛɵ ɩɹɬɚ ɨɤɚɡɵɜɚɥɢɫɶ ɜɧɭɬɪɢ ɞɢɧɚɦɢɱɟɫɤɨɝɨ ɢɧɬɟɪɜɚɥɚ. ȼ ɫɜɨɸ ɨɱɟɪɟɞɶ, ɤɨɥɢɱɟɫɬɜɨ ɧɚɧɟɫɟɧɧɨɝɨ ɛɟɥɤɚ ɹɜɥɹɟɬɫɹ ɮɭɧɤɰɢɟɣ ɱɢɫɥɚ ɤɥɟɬɨɤ.
95
4.2.2 Ȼɟɥɤɨɜɵɣ ɩɪɨɮɢɥɶ CD34+ ȽɋɄ
ȽɋɄ ɱɟɥɨɜɟɤɚ ɨɛɧɚɪɭɠɟɧɵ ɜ ɩɨɩɭɥɹɰɢɢ ɤɥɟɬɨɤ, ɷɤɫɩɪɟɫɫɢɪɭɸɳɢɯ ɜɵɫɨɤɢɣ ɭɪɨɜɟɧɶ ɚɧɬɢɝɟɧɚ CD34 (CD34+), ɯɨɬɹ ɨɞɧɢɦ ɢɡ ɞɪɭɝɢɯ
ɤɪɢɬɟɪɢɟɜ ɹɜɥɹɟɬɫɹ ɨɬɫɭɬɫɬɜɢɟ ɚɧɬɢɝɟɧɚ CD38 (CD38–) ɢ, ɬɚɤɢɦ ɨɛɪɚɡɨɦ, ɢɫɬɢɧɧɵɟ ȽɋɄ ɨɩɪɟɞɟɥɹɸɬɫɹ ɤɚɤ CD34+CD38– (55). Ɉɛɵɱɧɨɣ
ɩɪɚɤɬɢɤɨɣ ɹɜɥɹɟɬɫɹ ɪɚɫɫɦɚɬɪɢɜɚɬɶ ȽɋɄ ɤɚɤ CD34+ ɜ ɫɜɹɡɢ ɫ ɬɟɦ, ɱɬɨ
ɨɛɧɚɪɭɠɟɧɢɟ ɚɧɬɢɝɟɧɚ CD34 ɩɪɟɞɲɟɫɬɜɭɟɬ ɬɪɚɧɫɩɥɚɧɬɚɰɢɢ ɜ ɤɥɢɧɢɤɟ
ɢ ɫɨɡɞɚɧɢɸ ɛɚɧɤɚ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ.
Ⱦɥɹ ɰɟɥɟɣ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ ɩɪɢɧɹɬɨ ɧɚɡɜɚɧɢɟ «ɩɨɩɭɥɹɰɢɹ
CD34+ ȽɋɄ», ɜɤɥɸɱɚɸɳɚɹ ɤɥɟɬɤɢ CD38+ ɢ CD38–. Ɉɞɧɨɣ ɢɡ ɝɥɚɜɧɵɯ
ɩɪɢɱɢɧ ɞɥɹ ɷɬɨɝɨ ɹɜɥɹɟɬɫɹ ɬɨɬ ɮɚɤɬ, ɱɬɨ ɭɞɚɥɟɧɢɟ CD38+ ɤɥɟɬɨɤ ɩɪɢɜɨɞɢɬ ɤ ɩɚɞɟɧɢɸ ɨɛɳɟɝɨ ɱɢɫɥɚ ɤɥɟɬɨɤ ɧɢɠɟ ɦɢɧɢɦɭɦɚ (2×106), ɧɟɨɛɯɨɞɢɦɨɝɨ ɞɥɹ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ.
ɋ ɭɱɟɬɨɦ ɬɨɝɨ ɮɚɤɬɚ, ɱɬɨ ɤɥɢɧɢɰɢɫɬɵ ɬɪɚɧɫɩɥɚɧɬɢɪɭɸɬ ɜɟɫɶ ɨɛɪɚɡɟɰ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ, ɤɨɬɨɪɵɣ ɜɤɥɸɱɚɟɬ ɜ ɫɜɨɣ ɫɨɫɬɚɜ ɦɧɨɝɨɹɞɟɪɧɵɟ ɤɥɟɬɤɢ, ɆɇɄ (ɧɟɤɨɬɨɪɵɟ ɢɡ ɤɨɬɨɪɵɯ ɹɜɥɹɸɬɫɹ CD34– ɢ CD38+),
ɩɪɨɬɟɨɦɧɵɣ ɚɧɚɥɢɡ, ɫɨɡɞɚɧɧɵɣ ɞɥɹ ɢɡɭɱɟɧɢɹ ɤɥɟɬɨɤ CD34+, ɞɚɟɬ ɮɚɤɬɢɱɟɫɤɢɟ ɯɚɪɚɤɬɟɪɢɫɬɢɤɢ ɷɬɢɯ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɢ ɩɨɡɜɨɥɹɟɬ ɥɭɱɲɟ
ɩɨɧɹɬɶ ɫɜɨɣɫɬɜɚ ȽɋɄ.
ɋ ɞɪɭɝɨɣ ɫɬɨɪɨɧɵ, ɦɨɠɧɨ ɧɚɣɬɢ ɢ ɛɢɨɥɨɝɢɱɟɫɤɨɟ ɨɛɴɹɫɧɟɧɢɟ ɢ
ɩɪɟɞɩɨɥɨɠɢɬɶ, ɱɬɨ ɬɚɤɨɟ ɬɪɟɛɨɜɚɧɢɟ ɤ ɤɨɥɢɱɟɫɬɜɭ ɤɥɟɬɨɤ CD34+
ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɨɫɬɟɨɛɥɚɫɬɚɦɢ ɢ ɆɇɄ ɨɛɴɹɫɧɹɟɬɫɹ ɫɚɪɤɨɦɧɨɣ
ɩɪɢɪɨɞɨɣ ɤɥɟɬɨɤ MG63 ɢ ɛɨɥɶɲɟɣ ɡɪɟɥɨɫɬɶɸ ɆɇɄ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ
CD34+ ɤɥɟɬɤɚɦɢ, ɤɨɬɨɪɵɟ ɢɦɟɸɬ ɢ ɛɨɥɟɟ ɧɢɡɤɢɣ ɭɪɨɜɟɧɶ ɛɟɥɤɚ.
ɉɪɢɱɢɧɚ ɞɥɹ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɩɨɤɚɡɚɬɟɥɹ «ɱɢɫɥɨ ɤɥɟɬɨɤ», ɚ ɧɟ «ɚɛɫɨɥɸɬɧɨɟ ɤɨɥɢɱɟɫɬɜɨ ɛɟɥɤɚ» – ɛɨɥɟɟ ɚɞɟɤɜɚɬɧɨɟ ɩɪɟɞɫɬɚɜɥɟɧɢɟ ɢɫɫɥɟɞɭɟɦɨɣ ɤɥɟɬɨɱɧɨɣ ɩɨɩɭɥɹɰɢɢ, ɩɪɢɱɟɦ ɩɪɢɧɢɦɚɟɬɫɹ ɜɨ ɜɧɢɦɚɧɢɟ ɢ ɤɨ-
96
ɥɢɱɟɫɬɜɨ ɛɟɥɤɚ. Ʉ ɬɨɦɭ ɠɟ ɩɨɞɯɨɞ «ɱɢɫɥɨ ɤɥɟɬɨɤ» ɩɨɡɜɨɥɹɟɬ ɭɱɢɬɵɜɚɬɶ ɧɟ ɬɨɥɶɤɨ ɬɚɤɢɟ ɞɨɦɢɧɢɪɭɸɳɢɟ ɛɟɥɤɢ, ɤɚɤ ɚɥɶɛɭɦɢɧ, ɧɨ ɢ ɦɟɧɟɟ
ɡɚɦɟɬɧɵɟ, ɤɨɬɨɪɵɟ ɦɨɝɥɢ ɛɵ ɛɵɬɶ ɭɬɟɪɹɧɵ ɩɪɢ ɫɧɢɠɟɧɢɢ ɤɨɧɰɟɧɬɪɚɰɢɢ ɛɟɥɤɨɜ ɞɨ ɬɪɟɛɭɟɦɨɣ ɜɟɥɢɱɢɧɵ. Ɉɩɬɢɦɚɥɶɧɨɟ ɜɧɟɫɟɧɢɟ ɨɛɪɚɡɰɚ ɜ
ɝɟɥɶ, ɬɚɤɢɦ ɨɛɪɚɡɨɦ, ɛɭɞɟɬ ɡɚɜɢɫɟɬɶ ɨɬ ɭɪɨɜɧɹ ɷɤɫɬɪɚɝɢɪɨɜɚɧɧɨɝɨ ɛɟɥɤɚ ɤɚɤ ɮɭɧɤɰɢɢ ɢɫɩɨɥɶɡɨɜɚɧɧɨɝɨ ɱɢɫɥɚ ɤɥɟɬɨɤ. Ȼɨɥɟɟ ɬɨɝɨ, ɩɨɞɫɱɟɬ
ɤɥɟɬɨɤ ɛɨɥɟɟ ɫɨɜɦɟɫɬɢɦ ɫ ɚɥɝɨɪɢɬɦɨɦ ɚɧɚɥɢɡɚ, ɥɟɝɱɟ ɤɨɧɬɪɨɥɢɪɭɟɬɫɹ
ɢ ɩɪɢɫɩɨɫɨɛɥɟɧ ɞɥɹ ɢɡɭɱɟɧɢɹ ɤɭɥɶɬɭɪɵ ɤɥɟɬɨɤ, ɝɞɟ ɢɯ ɩɨɞɫɱɟɬ – ɪɭɬɢɧɧɚɹ ɩɪɨɰɟɞɭɪɚ. ɉɨɤɚɡɚɬɟɥɶ «ɱɢɫɥɨ ɤɥɟɬɨɤ» ɨɛɟɫɩɟɱɢɜɚɟɬ ɛɨɥɶɲɭɸ
ɭɧɢɜɟɪɫɚɥɶɧɨɫɬɶ ɢ ɫɬɚɧɞɚɪɬɢɡɚɰɢɸ ɤɥɟɬɨɱɧɨɝɨ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ.
ɑɢɫɥɨ ɤɥɟɬɨɤ, ɬɪɟɛɭɟɦɵɯ ɞɥɹ ɚɧɚɥɢɡɚ CD34+ ȽɋɄ, ɫɨɫɬɚɜɥɹɟɬ 2×106,
ɱɬɨ ɫɨɨɬɜɟɬɫɬɜɭɟɬ ɞɜɭɦ ɨɛɪɚɡɰɚɦ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ. Ɉɛɪɚɡɰɵ ɩɪɨɯɨɞɹɬ ɩɪɨɰɟɞɭɪɭ ɨɛɴɟɞɢɧɟɧɢɹ ɩɨɫɥɟ ɫɬɚɞɢɢ ɦɚɝɧɢɬɧɨɣ ɫɟɩɚɪɚɰɢɢ ɢ ɩɪɢɝɨɞɧɵ ɞɥɹ ɩɨɥɭɱɟɧɢɹ ɯɚɪɚɤɬɟɪɢɫɬɢɤ ɩɨɩɭɥɹɰɢɢ CD34+ ȽɋɄ.
Ʉɚɠɞɵɣ ɨɛɪɚɡɟɰ ɩɭɩɨɜɢɧɧɨɣ ɤɪɨɜɢ ɛɟɪɟɬɫɹ ɨɬ ɨɞɧɨɝɨ ɧɨɜɨɪɨɠɞɟɧɧɨɝɨ ɞɨɧɨɪɚ, ɩɨɷɬɨɦɭ ɨɛɴɟɞɢɧɟɧɢɟ ɨɛɪɚɡɰɨɜ ɨɡɧɚɱɚɟɬ, ɱɬɨ ɚɧɚɥɢɡ
ɨɬɪɚɠɚɟɬ ɪɟɡɭɥɶɬɚɬɵ ɞɜɭɯ ɢɧɞɢɜɢɞɭɭɦɨɜ. Ɍɚɤɨɣ ɷɮɮɟɤɬ ɨɛɴɟɞɢɧɟɧɢɹ
ɢɫɤɥɸɱɚɟɬ ɜɨɡɦɨɠɧɨɫɬɶ ɪɟɝɢɫɬɪɚɰɢɢ ɪɚɡɥɢɱɢɣ ɦɟɠɞɭ ɢɧɞɢɜɢɞɭɭɦɚɦɢ, ɧɨ ɩɨɡɜɨɥɹɟɬ ɩɪɨɜɨɞɢɬɶ ɞɟɬɚɥɢɡɢɪɨɜɚɧɧɨɟ ɨɩɢɫɚɧɢɟ ɩɨɩɭɥɹɰɢɢ
CD34+ ȽɋɄ ɱɟɥɨɜɟɤɚ.
ȿɫɥɢ ɧɟɨɛɯɨɞɢɦɨ ɩɪɨɜɟɫɬɢ ɪɚɡɦɧɨɠɟɧɢɟ CD34+ ȽɋɄ in vitro, ɫɥɟɞɭɟɬ ɢɫɩɨɥɶɡɨɜɚɬɶ ɩɪɨɬɟɨɦɧɵɣ ɩɪɨɮɢɥɶ ɨɛɟɡɥɢɱɟɧɧɨɝɨ ɨɛɪɚɡɰɚ ɤɚɤ
ɷɬɚɥɨɧ ɫɪɚɜɧɟɧɢɹ. Ɍɚɤɨɣ ɩɨɞɯɨɞ ɧɚɩɨɦɢɧɚɟɬ ɦɟɬɨɞɨɥɨɝɢɸ ɢɡɭɱɟɧɢɹ ɝɟɧɨɦɚ, ɩɪɢ ɤɨɬɨɪɨɣ ɨɩɪɟɞɟɥɹɟɬɫɹ ɩɨɫɥɟɞɨɜɚɬɟɥɶɧɨɫɬɶ ȾɇɄ ɜ
ɨɛɟɡɥɢɱɟɧɧɵɯ ɨɛɪɚɡɰɚɯ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɩɨɥɭɱɚɟɦɵɟ ɪɟɡɭɥɶɬɚɬɵ
ɫɨɨɬɜɟɬɫɬɜɭɸɬ ɨɩɢɫɚɧɢɸ ɩɨɩɭɥɹɰɢɢ CD34 +ȽɋɄ ɥɸɞɟɣ ɜ ɰɟɥɨɦ.
Ȼɨɥɟɟ ɬɨɝɨ, ɢɫɩɨɥɶɡɨɜɚɧɢɟ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɹ ɩɨɡɜɨɥɹɟɬ ɥɭɱɲɟ
ɨɯɚɪɚɤɬɟɪɢɡɨɜɚɬɶ ɪɚɡɧɵɟ ɛɟɥɤɢ ɢ ɞɚɬɶ ɛɨɥɟɟ ɩɨɥɧɭɸ ɤɚɪɬɢɧɭ ɩɪɨ97
ɬɟɨɦɧɨɝɨ ɩɪɨɮɢɥɹ ɩɨɩɭɥɹɰɢɢ CD34+ ȽɋɄ, ɬɨ ɟɫɬɶ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɬɶ ɛɟɥɤɢ, ɢɡ ɤɨɬɨɪɵɯ ɫɨɫɬɨɢɬ CD34+ ɫɬɜɨɥɨɜɚɹ ɤɥɟɬɤɚ ɢ ɩɨɧɹɬɶ
ɢɯ ɮɭɧɤɰɢɨɧɚɥɶɧɵɟ ɨɫɨɛɟɧɧɨɫɬɢ, ɚ ɬɚɤɠɟ ɩɨɩɵɬɚɬɶɫɹ ɜɵɹɫɧɢɬɶ
ɡɧɚɱɟɧɢɟ ɧɟɤɨɬɨɪɵɯ ɮɚɤɬɨɪɨɜ, ɜɥɢɹɸɳɢɯ ɧɚ ɜɨɡɧɢɤɧɨɜɟɧɢɟ ɢ ɪɚɡɜɢɬɢɟ ɷɬɢɯ ɭɧɢɤɚɥɶɧɵɯ ɤɥɟɬɨɤ.
Ƚɥɚɜɧɚɹ ɬɪɭɞɧɨɫɬɶ, ɩɪɟɩɹɬɫɬɜɭɸɳɚɹ ɢɫɫɥɟɞɨɜɚɧɢɸ ȽɋɄ –
ɧɢɡɤɚɹ ɞɨɫɬɭɩɧɨɫɬɶ ɬɚɤɢɯ ɤɥɟɬɨɤ ɢ, ɨɫɨɛɟɧɧɨ, ɦɚɥɵɟ ɤɨɥɢɱɟɫɬɜɚ
CD34+ ȽɋɄ. Ɍɨɱɧɟɟ, ɩɪɨɛɥɟɦɚ ɧɟ ɜ ɤɨɥɢɱɟɫɬɜɟ ɞɨɫɬɭɩɧɵɯ ɤɥɟɬɨɤ, ɚ
ɜ ɫɥɨɠɧɨɫɬɢ ɫɪɚɜɧɟɧɢɹ ɛɟɥɤɨɜɵɯ ɩɪɨɮɢɥɟɣ, ɩɨɥɭɱɟɧɧɵɯ ɫ ɩɨɦɨɳɶɸ 2D/MALDI-ɩɪɨɬɟɨɦɢɤɢ, ɞɥɹ ɤɥɟɬɨɱɧɵɯ ɩɨɩɭɥɹɰɢɣ ɩɪɢ ɨɝɪɚɧɢɱɟɧɧɨɦ ɱɢɫɥɟ ɤɥɟɬɨɤ. ɉɨɩɵɬɤɢ ɨɫɭɳɟɫɬɜɢɬɶ ɩɪɢɜɨɞɹɬ ɤ ɫɨɦɧɢɬɟɥɶɧɨɣ ɞɨɫɬɨɜɟɪɧɨɫɬɢ ɩɨɥɭɱɟɧɧɵɯ ɪɟɡɭɥɶɬɚɬɨɜ ɢ ɧɟɪɚɰɢɨɧɚɥɶɧɨɦɭ ɢɫɩɨɥɶɡɨɜɚɧɢɸ ɞɨɪɨɝɨɫɬɨɹɳɢɯ ɨɛɪɚɡɰɨɜ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ.
Ɉɞɢɧ ɢɡ ɦɟɬɨɞɢɱɟɫɤɢɯ ɩɨɞɯɨɞɨɜ ɞɥɹ ɪɟɲɟɧɢɹ ɩɪɨɛɥɟɦɵ ɞɨɫɬɭɩɧɨɫɬɢ ȽɋɄ – ɢɫɩɨɥɶɡɨɜɚɧɢɟ ɞɥɹ ɢɯ ɪɚɡɦɧɨɠɟɧɢɹ Jag1, ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɨɝɨ
ɧɚ ɦɢɤɪɨɫɮɟɪɚɯ. Kertesz ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ [48] ɩɨɤɚɡɚɥ, ɱɬɨ ɷɬɢ ɦɢɤɪɨɫɮɟɪɵ ɫɩɨɫɨɛɫɬɜɭɸɬ 2-ɤɪɚɬɧɨɦɭ ɭɜɟɥɢɱɟɧɢɸ ɱɢɫɥɚ ɦɵɲɢɧɵɯ ȽɋɄ ɜ
ɤɭɥɶɬɭɪɟ ɜ ɬɟɱɟɧɢɟ 14 ɞɧɟɣ. ɇɟɹɫɧɨ, ɨɞɧɚɤɨ, ɛɭɞɟɬ ɥɢ ɷɬɨɬ ɷɮɮɟɤɬ
ɜɨɫɩɪɨɢɡɜɟɞɟɧ ɧɚ ɤɥɟɬɤɚɯ ɱɟɥɨɜɟɤɚ ɢ ɤɚɤɨɜɵ ɛɭɞɭ ɫɜɨɣɫɬɜɚ ɩɨɥɭɱɟɧɧɨɣ ɩɨɩɭɥɹɰɢɢ, ɫɨɯɪɚɧɹɬ ɥɢ ɬɚɤɢɟ ɤɥɟɬɤɢ ɫɜɨɢ ɫɜɨɣɫɬɜɚ. ɂɦɟɧɧɨ ɩɪɨɬɟɨɦɢɤɚ ɛɭɞɟɬ ɫɩɨɫɨɛɫɬɜɨɜɚɬɶ ɩɨɥɭɱɟɧɢɸ ɨɬɜɟɬɚ ɧɚ ɷɬɢ ɜɨɩɪɨɫɵ.
ɉɨ ɧɚɲɟɦɭ ɦɧɟɧɢɸ, ɩɪɨɬɟɨɦɢɤɚ ɨɫɬɚɟɬɫɹ ɨɞɧɢɦ ɢɡ ɧɚɢɛɨɥɟɟ
ɦɨɳɧɵɯ ɢɧɫɬɪɭɦɟɧɬɨɜ ɢɡɭɱɟɧɢɹ ɛɟɥɤɨɜɨɣ ɷɤɫɩɪɟɫɫɢɢ. Ɉɱɟɧɶ ɜɚɠɧɨ
ɞɥɹ ɞɚɥɶɧɟɣɲɟɣ ɪɚɛɨɬɵ ɩɪɚɜɢɥɶɧɨ ɜɵɛɪɚɬɶ ɩɨɩɭɥɹɰɢɸ ɤɥɟɬɨɤ, ɬɚɤ ɤɚɤ
ɩɪɨɬɟɨɦɢɤɚ ɢɫɫɥɟɞɭɟɬ ɢɦɟɧɧɨ ɩɨɩɭɥɹɰɢɢ, ɚ ɧɟ ɟɞɢɧɢɱɧɵɟ ɤɥɟɬɤɢ. ɉɨɷɬɨɦɭ ɝɨɦɨɝɟɧɧɨɫɬɶ ɩɨɩɭɥɹɰɢɢ ɤɪɢɬɢɱɧɚ ɞɥɹ ɩɨɥɭɱɟɧɢɹ ɪɟɡɭɥɶɬɚɬɨɜ,
ɨɬɪɚɠɚɸɳɢɯ ɟɟ ɛɟɥɤɨɜɭɸ ɫɭɳɧɨɫɬɶ.
98
Ɉɞɧɨ ɢɡ ɧɚɩɪɚɜɥɟɧɢɣ ɩɟɪɫɩɟɤɬɢɜɧɵɯ ɞɚɥɶɧɟɣɲɢɯ ɢɫɫɥɟɞɨɜɚɧɢɣ –
ɢɡɭɱɟɧɢɟ ɤɭɥɶɬɭɪɵ CD34+ ɤɥɟɬɨɤ ɜ ɩɪɢɫɭɬɫɬɜɢɢ ɢ ɨɬɫɭɬɫɬɜɢɢ Jag1ɦɢɤɪɨɫɮɟɪ, ɱɬɨ ɨɛɟɳɚɟɬ ɩɨɥɭɱɟɧɢɟ ɢɧɮɨɪɦɚɰɢɢ ɨ ɛɟɥɤɚɯ, ɫɜɹɡɚɧɧɵɯ ɫ
ɪɚɡɦɧɨɠɟɧɢɟɦ ɬɚɤɢɯ ɤɥɟɬɨɤ.
ɉɪɨɬɟɨɦɢɤɚ, ɨɫɧɨɜɚɧɧɚɹ ɧɚ ɢɫɩɨɥɶɡɨɜɚɧɢɢ 2D/MALDI, ɬɪɟɛɭɟɬ
ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɞɨɫɬɚɬɨɱɧɨ ɛɨɥɶɲɢɯ ɨɛɴɟɦɨɜ ɛɟɥɤɚ ɜ ɢɫɫɥɟɞɭɟɦɵɯ ɨɛɪɚɡɰɚɯ. Ʉɚɤ ɭɠɟ ɭɤɚɡɵɜɚɥɨɫɶ, ɩɪɨɬɟɨɦɢɤɚ ɞɚɟɬ ɫɜɟɞɟɧɢɹ ɨ ɤɥɟɬɨɱɧɨɣ
ɩɨɩɭɥɹɰɢɢ, ɚ ɧɟ ɨɛ ɨɬɞɟɥɶɧɵɯ ɤɥɟɬɤɚɯ.
Ʉɨɧɬɪɨɥɢɪɭɹ ɢɡɦɟɧɟɧɢɹ ɜ ɛɟɥɤɚɯ, ɫ ɩɨɦɨɳɶɸ ɦɟɬɨɞɨɜ ɩɪɨɬɟɨɦɢɤɢ ɦɨɠɧɨ ɢɡɭɱɚɬɶ ɮɭɧɤɰɢɨɧɢɪɨɜɚɧɢɟ ɤɥɟɬɤɢ. ɗɬɢ ɢɡɦɟɧɟɧɢɟ ɦɨɠɧɨ
ɢɧɞɭɰɢɪɨɜɚɬɶ, ɢɡɦɟɧɹɹ ɭɫɥɨɜɢɹ ɜ ɤɭɥɶɬɭɪɟ ɤɥɟɬɨɤ in vitro, ɜ ɱɚɫɬɧɨɫɬɢ, ɫɩɨɫɨɛɫɬɜɭɹ ɭɜɟɥɢɱɟɧɢɸ ɫɬɜɨɥɨɜɨɫɬɢ ɤɥɟɬɨɤ. Ɍɟɫɬɢɪɭɹ ɫɬɜɨɥɨɜɨɫɬɶ ɤɥɟɬɨɤ, ɦɵ ɩɨɥɭɱɚɟɦ ɫɩɨɫɨɛɧɨɫɬɶ ɨɛɧɚɪɭɠɢɜɚɬɶ ɤɥɸɱɟɜɵɟ ɛɟɥɤɢ, ɜɨɜɥɟɱɟɧɧɵɟ ɜ ɪɟɝɭɥɹɰɢɸ ɢ ɩɨɞɞɟɪɠɚɧɢɟ ɷɬɨɣ ɜɚɠɧɟɣɲɟɣ ɮɭɧɤɰɢɢ.
ȽɋɄ ɨɛɵɱɧɨ ɤɭɥɶɬɢɜɢɪɭɸɬ in vitro ɜ ɤɨɦɛɢɧɚɰɢɢ ɫ ɪɚɡɥɢɱɧɵɦɢ
ɮɚɤɬɨɪɚɦɢ ɪɨɫɬɚ, ɚ ɢɦɟɧɧɨ: ɮɚɤɬɨɪɨɦ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ (SCF, 100
ng/ml); ɥɢɝɚɧɞɨɦ Flt-3 (100 ng/ml); ɬɪɨɦɛɨɩɨɷɬɢɧɨɦ (TPO, 50 ng/ml); ɂɧɬɟɪɥɟɣɤɢɧɨɦ-6 (IL-6, 100 ng/ml). ɗɬɢ ɮɚɤɬɨɪɵ, ɤɚɤ ɛɵɥɨ ɩɨɤɚɡɚɧɨ, ɩɨɞɞɟɪɠɢɜɚɸɬ ɩɨɩɭɥɹɰɢɸ CD34+/CD38–ɤɥɟɬɨɤ, ɨɩɪɟɞɟɥɹɟɦɭɸ ɩɨ ɦɟɦɛɪɚɧɨɚɫɫɨɰɢɢɪɨɜɚɧɧɵɦ ɦɚɪɤɟɪɚɦ ɫɬɜɨɥɨɜɨɫɬɢ. ɗɬɚ ɩɨɩɭɥɹɰɢɹ ɫɬɜɨɥɨɜɵɯ
ɤɥɟɬɨɤ ɦɨɠɟɬ ɛɵɬɶ ɞɨɩɨɥɧɢɬɟɥɶɧɨ ɫɬɢɦɭɥɢɪɨɜɚɧɚ ɩɪɢ ɢɫɩɨɥɶɡɨɜɚɧɢɢ
ɫɢɧɬɟɬɢɱɟɫɤɨɝɨ ɚɝɟɧɬɚ, ɦɵɲɢɧɨɝɨ ɪɟɤɨɦɛɢɧɚɧɬɧɨɝɨ ɩɟɩɬɢɞɚ (Jagged-1),
ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɨɝɨ ɧɚ ɩɨɜɟɪɯɧɨɫɬɢ BrCN-aɤɬɢɜɢɪɨɜɚɧɧɵɯ ɦɢɤɪɨɫɮɟɪ.
ɗɬɨɬ ɫɢɧɬɟɬɢɱɟɫɤɢɣ ɚɝɟɧɬ ɜɡɚɢɦɨɞɟɣɫɬɜɭɟɬ ɫ ɪɟɰɟɩɬɨɪɨɦ Notch-1, ɱɬɨ
ɜɵɡɵɜɚɟɬ ɚɤɬɢɜɚɰɢɸ Notch-1-ɨɩɨɫɪɟɞɨɜɚɧɧɨɣ ɬɪɚɧɫɞɭɤɰɢɢ ɫɢɝɧɚɥɚ. ɉɨɥɚɝɚɸɬ, ɱɬɨ ɝɟɧɟɪɢɪɨɜɚɧɧɵɣ ɦɨɥɟɤɭɥɹɪɧɵɣ ɫɢɝɧɚɥ ɫɩɟɰɢɮɢɱɟɧ ɞɥɹ
ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ ɢ ɜɤɥɸɱɚɟɬ ɦɧɨɝɨɱɢɫɥɟɧɧɵɟ ɛɟɥɤɢ, ɧɟɨɛɯɨɞɢɦɵɟ ɞɥɹ
99
ɩɨɞɞɟɪɠɚɧɢɹ ɫɬɜɨɥɨɜɨɫɬɢ. Ɂɚ ɷɬɢɦɢ ɫɨɛɵɬɢɹɦɢ ɢ ɢɯ ɫɨɫɬɚɜɥɹɸɳɢɦɢ
ɦɨɠɧɨ ɧɚɛɥɸɞɚɬɶ ɫ ɩɨɦɨɳɶɸ ɨɩɢɫɚɧɧɵɯ ɜ ɪɚɛɨɬɟ ɦɟɬɨɞɨɜ ɩɪɨɬɟɨɦɢɤɢ.
ɉɨɬɟɧɰɢɚɥ ɩɪɨɬɟɨɦɢɤɢ ɫɜɹɡɵɜɚɸɬ ɫ ɬɳɚɬɟɥɶɧɵɦ ɨɩɢɫɚɧɢɟɦ ɛɟɥɤɨɜɨɝɨ ɩɪɨɮɢɥɹ ɤɥɟɬɨɱɧɵɯ ɩɨɩɭɥɹɰɢɣ. ɉɪɨɬɟɨɦɢɤɚ ɜɪɹɞ ɥɢ ɩɪɟɞɧɚɡɧɚɱɟɧɚ ɞɥɹ ɧɚɛɥɸɞɟɧɢɹ ɡɚ ɬɨɧɤɢɦɢ ɢɡɦɟɧɟɧɢɹɦɢ ɷɤɫɩɪɟɫɫɢɢ. Ȼɨɥɟɟ
ɰɟɥɟɫɨɨɛɪɚɡɧɨ ɢɫɩɨɥɶɡɨɜɚɬɶ ɟɟ ɞɥɹ ɨɩɪɟɞɟɥɟɧɢɹ ɢ ɞɢɮɮɟɪɟɧɰɢɚɰɢɢ
ɤɥɟɬɨɱɧɵɯ ɫɭɛɩɨɩɭɥɹɰɢɣ. ɂɫɬɢɧɧɵɟ ɜɨɡɦɨɠɧɨɫɬɢ ɩɪɨɬɟɨɦɢɤɢ, ɦɚɥɨɞɨɫɬɭɩɧɵɟ ɞɥɹ ɞɪɭɝɢɯ ɦɟɬɨɞɨɜ ɧɚɛɥɸɞɟɧɢɹ ɡɚ ɷɤɫɩɪɟɫɫɢɟɣ ɛɟɥɤɨɜ, ɡɚɤɥɸɱɚɸɬɫɹ ɜ ɨɛɧɚɪɭɠɟɧɢɢ ɩɨɫɬɬɪɚɧɫɥɹɰɢɨɧɧɵɯ ɦɨɞɢɮɢɤɚɰɢɣ (ɧɚɩɪɢɦɟɪ, ɮɨɫɮɨɪɢɥɢɪɨɜɚɧɢɹ). Ⱦɪɭɝɨɟ ɞɨɫɬɨɢɧɫɬɜɨ ɩɪɨɬɟɨɦɢɤɢ ɜ ɫɨɱɟɬɚɧɢɢ
ɫ ɛɢɨɢɧɮɨɪɦɚɬɢɤɨɣ – ɫɩɨɫɨɛɧɨɫɬɶ ɢɡɭɱɚɬɶ ɤɥɟɬɤɭ ɢ ɤɚɤ ɰɟɥɨɟ, ɢ ɤɚɤ
ɨɬɞɟɥɶɧɵɟ ɟɟ ɤɨɦɩɚɪɬɦɟɧɬɵ, ɮɢɤɫɢɪɨɜɚɬɶ ɢɡɦɟɧɟɧɢɹ ɜ ɧɢɯ ɤɨɧɰɟɧɬɪɚɰɢɢ ɛɟɥɤɨɜ.
ɉɪɨɬɨɤɨɥ ɩɪɨɬɟɨɦɧɵɯ ɢɫɫɥɟɞɨɜɚɧɢɣ CD34+ ȽɋɄ ɛɵɥ ɚɜɬɨɦɚɬɢɡɢɪɨɜɚɧ ɧɚɦɢ ɫ ɰɟɥɶɸ ɦɚɤɫɢɦɚɥɶɧɨ ɜɨɡɦɨɠɧɨɝɨ ɩɨɜɵɲɟɧɢɹ ɜɨɫɩɪɨɢɡɜɨɞɢɦɨɫɬɢ ɢ ɢɫɤɥɸɱɟɧɢɹ ɨɲɢɛɨɱɧɨɝɨ ɜɥɢɹɧɢɹ ɱɟɥɨɜɟɱɟɫɤɨɝɨ ɮɚɤɬɨɪɚ. Ʉɥɸɱ ɤ ɤɚɪɬɢɪɨɜɚɧɢɸ ɜɫɟɝɨ ɩɪɨɬɟɨɦɚ ȽɋɄ ɥɟɠɚɬ ɜ ɚɜɬɨɦɚɬɢɡɚɰɢɢ ɩɪɨɬɨɤɨɥɚ ɬɚɤɢɦ ɨɛɪɚɡɨɦ, ɱɬɨ ɢɦɟɬɶ ɫɩɨɫɨɛɧɨɫɬɶ ɧɟ ɬɨɥɶɤɨ ɚɧɚɥɢɡɢɪɨɜɚɬɶ ɛɨɥɶɲɢɟ ɨɛɴɟɦɵ ɨɛɪɚɡɰɨɜ, ɧɨ ɢ ɩɨɞɞɟɪɠɢɜɚɬɶ ɜɵɫɨɤɢɣ
ɭɪɨɜɟɧɶ ɢɫɩɨɥɧɟɧɢɹ ɨɩɟɪɚɰɢɣ ɧɚ ɩɪɨɬɹɠɟɧɢɢ ɜɫɟɯ ɫɬɚɞɢɣ ɚɧɚɥɢɡɚ.
ɉɟɪɜɚɹ ɫɬɚɞɢɹ ɚɜɬɨɦɚɬɢɡɚɰɢɢ – ɢɡɜɥɟɱɟɧɢɟ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ ɢɡ ɝɟɥɹ. ɗɬɭ ɩɪɨɰɟɞɭɪɭ ɨɫɭɳɟɫɬɜɥɹɟɬ ɪɨɛɨɬ, ɜɵɪɟɡɚɸɳɢɣ ɩɹɬɧɨ ɥɟɡɜɢɟɦ
ɞɢɚɦɟɬɪɨɦ 2 ɦɦ, ɜ ɨɬɥɢɱɢɟ ɨɬ ɪɭɱɧɨɝɨ ɫɩɨɫɨɛɚ ɫ ɢɫɩɨɥɶɡɨɜɚɧɢɟɦ
ɫɤɚɥɶɩɟɥɹ. Ƚɥɚɜɧɨɟ ɩɪɟɢɦɭɳɟɫɬɜɨ ɚɜɬɨɦɚɬɢɡɚɰɢɢ ɜ ɞɚɧɧɨɦ ɫɥɭɱɚɟ –
ɜɨɡɦɨɠɧɨɫɬɶ ɢɡɜɥɟɱɟɧɢɹ ɛɨɥɶɲɨɝɨ ɤɨɥɢɱɟɫɬɜɚ ɩɹɬɟɧ, ɱɬɨ ɡɚɬɪɭɞɧɢɬɟɥɶɧɨ ɫɞɟɥɚɬɶ ɜɪɭɱɧɭɸ. Ⱦɪɭɝɨɟ ɩɪɟɢɦɭɳɟɫɬɜɨ ɫɨɫɬɨɢɬ ɜ ɬɨɦ, ɱɬɨ ɜɵɪɟɡɚɧɢɟ ɩɪɨɢɫɯɨɞɢɬ ɜ ɡɨɧɟ ɧɚɢɛɨɥɶɲɟɣ ɤɨɧɰɟɧɬɪɚɰɢɢ ɛɟɥɤɚ, ɤɨɬɨɪɨɟ
ɨɩɪɟɞɟɥɹɟɬɫɹ ɫ ɩɨɦɨɳɶɸ ɤɨɦɩɶɸɬɟɪɧɨɝɨ ɚɧɚɥɢɡɚ. ɗɬɨ ɩɨɡɜɨɥɹɟɬ
100
ɨɛɟɫɩɟɱɢɬɶ ɩɨɫɬɨɹɧɫɬɜɨ ɨɛɴɟɦɚ ɨɛɪɚɡɰɚ ɢ ɤɨɥɢɱɟɫɬɜɚ ɛɟɥɤɚ ɩɪɢ ɭɫɥɨɜɢɢ ɞɨɫɬɚɬɨɱɧɨɝɨ ɪɚɡɦɟɪɚ ɩɹɬɧɚ. ɉɪɢɦɟɧɟɧɢɟ ɥɟɡɜɢɹ ɬɚɤɠɟ ɫɩɨɫɨɛɫɬɜɭɟɬ ɧɟɪɚɡɪɭɲɟɧɢɸ ɫɨɫɟɞɧɢɯ ɩɹɬɟɧ. Ɍɟɦ ɧɟ ɦɟɧɟɟ, ɧɟɞɨɫɬɚɬɤɨɦ
ɪɨɛɨɬɚ ɞɚɧɧɨɣ ɤɨɧɫɬɪɭɤɰɢɢ (Gelpix, Genetix) ɹɜɥɹɟɬɫɹ ɩɨɩɚɞɚɧɢɟ ɝɟɥɹ ɧɚ ɥɟɡɜɢɟ, ɱɬɨ ɡɚɬɪɭɞɧɹɟɬ ɢɡɜɥɟɱɟɧɢɟ ɩɨɫɥɟɞɭɸɳɢɯ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ. ɗɬɨ ɩɪɟɩɹɬɫɬɜɢɟ ɭɫɬɪɚɧɹɟɬɫɹ ɡɚ ɫɱɟɬ ɩɨɫɬɨɹɧɧɨɝɨ ɩɪɨɦɵɜɚɧɢɹ
ɥɟɡɜɢɹ ɜɨɞɨɣ.
ȼɬɨɪɚɹ ɚɜɬɨɦɚɬɢɡɢɪɨɜɚɧɧɚɹ ɫɬɚɞɢɹ – ɪɨɛɨɬɢɡɚɰɢɹ (GE healthcare)
ɩɪɨɰɟɞɭɪɵ ɩɟɪɟɜɚɪɢɜɚɧɢɹ ɛɟɥɤɚ. Ɂɞɟɫɶ ɬɚɤɠɟ ɜɨɡɦɨɠɧɚ ɪɚɛɨɬɚ ɫ
ɛɨɥɶɲɢɦ ɤɨɥɢɱɟɫɬɜɨɦ ɛɟɥɤɨɜɵɯ ɩɹɬɟɧ. Ɉɞɧɚ ɢɡ ɩɪɨɛɥɟɦ ɩɪɢ ɢɫɩɨɥɶɡɨɜɚɧɢɢ ɷɬɨɝɨ ɪɨɛɨɬɚ – ɫɨɫɤɚɥɶɡɵɜɚɧɢɟ ɝɟɥɹ ɫ ɥɟɡɜɢɹ, ɩɪɟɞɨɬɜɪɚɳɚɟɦɨɟ ɭɫɬɪɚɧɟɧɢɟɦ ɢɡɛɵɬɨɱɧɨɣ ɠɢɞɤɨɫɬɢ ɡɚ ɫɱɟɬ ɟɟ ɢɫɩɚɪɟɧɢɹ. Ɉɞɧɚɤɨ
ɩɨɫɥɟɞɧɟɟ ɞɨɥɠɧɨ ɛɵɬɶ ɡɚɜɟɪɲɟɧɨ ɤ ɦɨɦɟɧɬɭ ɞɨɛɚɜɥɟɧɢɹ ɮɟɪɦɟɧɬɚ ɜɨ
ɢɡɛɟɠɚɧɢɟ ɩɨɬɟɪɶ ɩɨɥɢɩɟɩɬɢɞɨɜ, ɚɞɫɨɪɛɢɪɭɸɳɢɯɫɹ ɧɚ ɩɥɚɫɬɢɤɨɜɵɯ
ɫɬɟɧɤɚɯ ɫɨɫɭɞɚ.
ɉɨɫɥɟɞɧɹɹ ɢ ɮɢɧɚɥɶɧɚɹ ɫɬɚɞɢɹ ɚɜɬɨɦɚɬɢɡɚɰɢɢ – ɢɫɩɨɥɶɡɨɜɚɧɢɟ
ɪɨɛɨɬɚ Cartesian SynQuad, Genomic Solutions ɞɥɹ ɩɨɞɝɨɬɨɜɤɢ «ɫɷɧɞɜɢɱɚ» ɦɚɬɪɢɰɚ-ɨɛɪɚɡɟɰ (ɪɚɫɬɜɨɪ ɩɟɩɬɢɞɚ)-ɦɚɬɪɢɰɚ ɞɥɹ MADLI-ɚɧɚɥɢɡɚ.
ɂɬɚɤ, ɧɚɦɢ ɩɪɨɞɟɦɨɧɫɬɪɢɪɨɜɚɧɨ, ɱɬɨ ɤɨɦɛɢɧɚɰɢɹ 2D ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɫ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɟɦ ɤɥɟɬɨɱɧɵɯ ɨɪɝɚɧɟɥɥ ɦɨɠɟɬ ɞɚɬɶ ɢɧɮɨɪɦɚɰɢɸ ɨ ɜɧɭɬɪɢɤɥɟɬɨɱɧɨɣ ɥɨɤɚɥɢɡɚɰɢɢ ɫɩɟɰɢɮɢɱɟɫɤɢɯ ɛɟɥɤɨɜ. Ɋɚɡɪɚɛɨɬɚɧɧɵɣ ɦɟɬɨɞ ɨɬɥɢɱɚɟɬɫɹ ɜɨɫɩɪɨɢɡɜɨɞɢɦɨɫɬɶɸ ɢ ɜɨɡɦɨɠɧɨɫɬɶɸ ɤɨɥɢɱɟɫɬɜɟɧɧɨɣ ɨɰɟɧɤɢ ɪɟɡɭɥɶɬɚɬɨɜ. ȼɚɪɢɚɛɟɥɶɧɨɫɬɶ ɩɨɥɭɱɚɟɦɵɯ ɞɚɧɧɵɯ
ɫɧɢɠɟɧɚ, ɜ ɬɨɦ ɱɢɫɥɟ ɡɚ ɫɱɟɬ ɦɢɧɢɦɢɡɚɰɢɢ ɩɨɦɟɯɨɨɛɪɚɡɨɜɚɧɢɹ ɫɨ ɫɬɨɪɨɧɵ ɞɨɦɢɧɢɪɭɸɳɢɯ ɜ ɨɛɪɚɡɰɟ ɛɟɥɤɨɜ. ȼ ɢɞɟɚɥɶɧɨɦ ɫɥɭɱɚɟ, ɞɨɥɠɧɚ
ɛɵɬɶ ɜɨɡɦɨɠɧɨɫɬɶ ɚɜɬɨɦɚɬɢɡɚɰɢɢ ɜɫɟɝɨ ɧɚɛɨɪɚ ɩɪɨɰɟɞɭɪ.
ɂɫɫɥɟɞɨɜɚɧɢɟ ȽɋɄ ɫ ɩɨɦɨɳɶɸ ɩɪɨɬɟɨɦɢɤɢ ɩɨɡɜɨɥɹɟɬ ɩɨɥɭɱɢɬɶ
ɫɜɟɞɟɧɢɹ ɨ ɦɨɥɟɤɭɥɹɪɧɵɯ ɦɟɯɚɧɢɡɦɚɯ ɫɢɝɧɚɥɢɡɚɰɢɢ. ɇɚɩɪɢɦɟɪ, ɩɟɪɟ101
ɞɚɱɚ ɫɢɝɧɚɥɚ Notch1, ɤɨɬɨɪɵɣ ɚɤɬɢɜɢɪɭɟɬɫɹ Jag1 ɢ ɜɤɥɸɱɚɟɬ ɜ ɫɟɛɹ ɩɟɪɟɦɟɳɟɧɢɟ ɛɟɥɤɚ MAML1 ɢɡ ɰɢɬɨɩɥɚɡɦɵ ɜ ɹɞɪɨ, ɦɨɠɟɬ ɢɡɭɱɚɬɶɫɹ ɧɚ
ɭɪɨɜɧɟ ɪɚɡɧɵɯ ɤɥɟɬɨɱɧɵɯ ɮɪɚɤɰɢɣ ɩɪɢ ɢɡɦɟɪɟɧɢɢ ɭɪɨɜɧɟɣ ɛɟɥɤɚ ɢ/ɢɥɢ
ɷɤɫɩɪɟɫɫɢɢ ɧɨɜɵɯ ɛɟɥɤɨɜ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɩɨɞɬɜɟɪɠɞɚɸɬɫɹ ɢɡɜɟɫɬɧɵɟ
ɩɭɬɢ ɩɟɪɟɞɚɱɢ ɫɢɝɧɚɥɨɜ ɢɥɢ ɨɛɧɚɪɭɠɢɜɚɸɬɫɹ ɧɨɜɵɟ ɩɭɬɢ.
Ȼɨɥɟɟ ɬɨɝɨ, ɞɥɹ ɢɡɜɟɫɬɧɵɯ ɩɭɬɟɣ ɩɟɪɟɞɚɱɢ ɫɢɝɧɚɥɚ ɦɨɝɭɬ ɛɵɬɶ
ɪɚɫɫɱɢɬɚɧɵ ɬɟɨɪɟɬɢɱɟɫɤɢɟ ɡɧɚɱɟɧɢɹ pI ɢ MW ɛɟɥɤɨɜ-ɭɱɚɫɬɧɢɤɨɜ ɡɚ
ɫɱɟɬ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ɬɚɤɨɝɨ ɢɧɫɬɪɭɦɟɧɬɚ, ɤɚɤ «Compute pI/MW»
(http://www.expasy.org/tools/). Ɋɚɫɫɱɢɬɚɧɧɵɟ ɬɚɤɢɦ ɨɛɪɚɡɨɦ pI ɢ MW
ɞɥɹ MAML1 ɫɨɫɬɚɜɢɥɢ 8,45 ɢ 108 kDa ɫɨɨɬɜɟɬɫɬɜɟɧɧɨ. ɉɨ ɷɬɢɦ ɜɟɥɢɱɢɧɚɦ ɦɨɠɧɨ ɨɩɪɟɞɟɥɢɬɶ ɤɨɨɪɞɢɧɚɬɵ ɛɟɥɤɚ ɜ 2D-ɝɟɥɟ ɢ ɢɫɩɨɥɶɡɨɜɚɬɶ
ɷɬɨ ɞɥɹ ɞɨɩɨɥɧɢɬɟɥɶɧɨɝɨ ɚɧɚɥɢɡɚ. ɏɨɬɹ ɬɚɤɨɣ ɩɨɞɯɨɞ ɢ ɢɦɟɟɬ ɨɩɪɟɞɟɥɟɧɧɵɟ ɧɟɞɨɫɬɚɬɤɢ, ɤɨɬɨɪɵɟ ɩɨɬɪɟɛɭɸɬ ɭɫɢɥɢɣ ɩɨ ɭɫɬɪɚɧɟɧɢɸ, ɨɧ ɧɚɫɬɨɥɶɤɨ ɩɪɟɜɨɫɯɨɞɢɬ ɬɪɚɞɢɰɢɨɧɧɵɟ ɦɟɬɨɞɢɤɢ, ɱɬɨ ɪɚɫɫɦɚɬɪɢɜɚɟɬɫɹ
ɤɚɤ ɨɱɟɧɶ ɩɟɪɫɩɟɤɬɢɜɧɵɣ ɞɥɹ ɛɭɞɭɳɢɯ ɢɫɫɥɟɞɨɜɚɧɢɣ.
Ɍɟɦ ɧɟ ɦɟɧɟɟ, ɢ ɬɪɚɞɢɰɢɨɧɧɵɟ ɦɟɬɨɞɵ ɢɫɫɥɟɞɨɜɚɧɢɹ ɩɪɨɬɟɨɦɚ
ɤɥɟɬɨɱɧɨɣ ɩɨɩɭɥɹɰɢɢ ɧɟ ɢɫɱɟɪɩɚɥɢ ɫɜɨɢɯ ɜɨɡɦɨɠɧɨɫɬɟɣ ɞɥɹ ɢɡɭɱɟɧɢɹ
ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ. ȼ ɱɚɫɬɧɨɫɬɢ, ɨɧɢ ɦɨɝɭɬ ɛɵɬɶ ɢɫɩɨɥɶɡɨɜɚɧɵ ɞɥɹ
ɥɭɱɲɟɝɨ ɩɨɧɢɦɚɧɢɹ ɦɨɥɟɤɭɥɹɪɧɨɣ ɫɢɝɧɚɥɢɡɚɰɢɢ ɢ ɜɡɚɢɦɨɞɟɣɫɬɜɢɹ
ɛɟɥɤɨɜ ɞɪɭɝ ɫ ɞɪɭɝɨɦ.
ȼ ɰɟɥɨɦ, ɜ ȽɋɄ ɧɚɦ ɭɞɚɥɨɫɶ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɬɶ ɛɨɥɟɟ 500 ɛɟɥɤɨɜ
(ɩɪɟɞɫɬɚɜɥɟɧɵ ɜ ɩɪɢɥɨɠɟɧɢɢ), (ɜɤɥɸɱɚɹ ɢɡɨɮɨɪɦɵ ɢ ɩɨɫɬɬɪɚɧɫɥɹɰɢɨɧɧɵɟ ɦɨɞɢɮɢɤɚɰɢɢ), ɫɩɨɫɨɛɧɵɯ ɜɵɩɨɥɧɹɬɶ ɪɚɡɧɵɟ ɮɭɧɤɰɢɢ ɜ ɤɥɟɬɤɟ. ɉɨɥɭɱɟɧɧɚɹ ɩɪɨɬɟɨɦɧɚɹ ɤɚɪɬɚ ɹɜɥɹɟɬɫɹ ɩɨɥɟɡɧɵɦ ɢɧɫɬɪɭɦɟɧɬɨɦ,
ɫɩɨɫɨɛɫɬɜɭɸɳɢɦ ɨɰɟɧɢɜɚɬɶ ɫɨɫɬɨɹɧɢɟ ɜ ɤɥɟɬɨɤ ɜ ɧɨɪɦɟ ɢ ɩɚɬɨɥɨɝɢɢ ɜ
ɪɚɡɧɵɯ ɷɤɫɩɟɪɢɦɟɧɬɚɥɶɧɵɯ ɭɫɥɨɜɢɹɯ ɢ ɞɨɩɨɥɧɹɟɬ ɚɧɚɥɨɝɢɱɧɵɟ, ɪɚɧɟɟ
ɩɨɥɭɱɟɧɧɵɟ ɞɚɧɧɵɟ [12, 40, 57, 65, 77, 91, 92, 106,109].
102
4.3. ɉɪɨɬɟɨɦɢɤɚ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɢ ɩɟɪɫɩɟɤɬɢɜɵ ɢɫɩɨɥɶɡɨɜɚɧɢɹ
ȽɋɄ ɞɥɹ ɬɟɪɚɩɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ
ȼ ɰɟɥɹɯ ɥɭɱɲɟɣ ɢɧɬɟɪɩɪɟɬɚɰɢɢ ɪɟɡɭɥɶɬɚɬɨɜ, ɩɨɥɭɱɟɧɧɵɯ ɜ ɧɚɲɟɦ ɢɫɫɥɟɞɨɜɚɧɢɢ, ɩɪɟɞɫɬɚɜɥɹɟɬɫɹ ɰɟɥɟɫɨɨɛɪɚɡɧɵɦ ɜɡɹɬɶ ɡɚ ɨɫɧɨɜɭ
ɨɞɧɭ ɢɡ ɤɨɧɰɟɩɰɢɣ ɪɚɡɜɢɬɢɹ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɨɬ ɧɚɱɚɥɶɧɵɯ ɫɬɚɞɢɣ ɞɨ
ɫɨɫɬɨɹɧɢɹ ɜɵɪɚɠɟɧɧɨɣ ɩɚɬɨɥɨɝɢɢ.
ȼ ɫɨɨɬɜɟɬɫɬɜɢɢ ɫ ɧɟɣ, ɤɨɦɩɥɟɤɫɧɚɹ ɫɢɫɬɟɦɚ ɪɟɩɚɪɚɰɢɢ ɚɪɬɟɪɢɣ
ɜɤɥɸɱɚɟɬ ɤɚɤ ɥɨɤɚɥɶɧɵɟ, ɬɚɤ ɢ ɩɪɨɢɫɯɨɞɹɳɢɟ ɢɡ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɤɥɟɬɤɢ, ɨɛɟɫɩɟɱɢɜɚɸɳɢɟ ɝɨɦɟɨɫɬɚɡ ɢ ɰɟɥɨɫɬɧɨɫɬɶ ɫɨɫɭɞɨɜ. Ɂɚɜɢɫɹɳɢɣ ɨɬ
ɜɨɡɪɚɫɬɚ ɨɬɤɚɡ ɤɨɫɬɧɨɝɨ ɦɨɡɝɚ ɩɪɨɞɭɰɢɪɨɜɚɬɶ ɫɨɫɭɞɢɫɬɵɟ ɩɪɨɝɟɧɢɬɨɪɧɵɟ ɤɥɟɬɤɢ, ɨɬɜɟɬɫɬɜɟɧɧɵɟ ɡɚ ɜɨɫɫɬɚɧɨɜɥɟɧɢɟ ɚɪɬɟɪɢɣ – ɧɟɫɩɨɫɨɛɧɨɫɬɶ, ɤɨɬɨɪɚɹ ɜɵɡɜɚɧɚ ɞɥɹɳɢɦɢɫɹ ɜ ɬɟɱɟɧɢɟ ɜɫɟɣ ɠɢɡɧɢ ɮɚɤɬɨɪɚɦɢ,
ɬɚɤɢɦɢ, ɤɚɤ ɝɢɩɟɪɥɢɩɢɞɟɦɢɹ, ɫɩɨɫɨɛɫɬɜɭɟɬ ɪɚɡɜɢɬɢɸ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɢ
ɟɝɨ ɬɪɨɦɛɨɷɦɛɨɥɢɱɟɫɤɢɯ ɨɫɥɨɠɧɟɧɢɣ.
Ʉɚɤ ɩɨɫɥɟɞɫɬɜɢɟ ɬɚɤɨɝɨ ɨɬɤɚɡɚ, ɧɨɪɦɚɥɶɧɵɣ ɩɪɨɰɟɫɫ ɜɨɫɫɬɚɧɨɜɥɟɧɢɹ ɚɪɬɟɪɢɚɥɶɧɨɣ ɫɬɟɧɤɢ ɧɚɪɭɲɚɟɬɫɹ. ɇɚɪɭɲɟɧɢɟ ɪɚɜɧɨɜɟɫɢɹ ɦɟɠɞɭ ɩɨɜɪɟɠɞɟɧɢɟɦ ɚɪɬɟɪɢɚɥɶɧɨɣ ɫɬɟɧɤɢ ɢ ɟɟ ɜɨɫɫɬɚɧɨɜɥɟɧɢɟɦ ɜɟɞɟɬ ɤ
ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɦɭ ɜɨɫɩɚɥɟɧɢɸ ɢ ɩɨɫɥɟɞɭɸɳɢɦ ɨɫɥɨɠɧɟɧɢɹɦ. Ʉɨɫɬɧɵɣ ɦɨɡɝ ɢ ɩɪɨɢɫɯɨɞɹɳɢɟ ɢɡ ɧɟɝɨ ɋɄ ɩɪɟɞɫɬɚɜɥɹɸɬ ɫɨɛɨɣ ɤɥɸɱɟɜɵɟ ɪɟɝɭɥɹɬɨɪɵ ɚɬɟɪɨɫɤɥɟɪɨɡɚ, ɢ ɩɪɨɝɪɟɫɫ ɜ ɩɪɟɞɨɬɜɪɚɳɟɧɢɢ ɢ ɥɟɱɟɧɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɢ ɟɝɨ ɬɪɨɦɛɨɷɦɛɨɥɢɱɟɫɤɢɯ ɨɫɥɨɠɧɟɧɢɣ ɞɨɥɠɟɧ
ɨɫɭɳɟɫɬɜɥɹɬɶɫɹ ɫ ɭɱɟɬɨɦ ɷɬɨɝɨ ɢɡɦɟɪɟɧɢɹ ɩɪɨɰɟɫɫɚ ɛɨɥɟɡɧɢ [19].
Ȼɟɥɤɢ ɋɄ, ɰɢɪɤɭɥɢɪɭɸɳɢɯ ɜ ɤɪɨɜɢ, ɦɨɝɭɬ ɫɥɭɠɢɬɶ ɢ ɞɢɚɝɧɨɫɬɢɱɟɫɤɢɦɢ ɦɚɪɤɟɪɚɦɢ ɞɥɹ ɩɪɟɞɫɤɚɡɚɧɢɹ ɨɬɧɨɫɢɬɟɥɶɧɨɝɨ ɪɢɫɤɚ ɪɚɡɜɢɬɢɹ
ɚɬɟɪɨɫɤɥɟɪɨɡɚ, ɢ ɢɫɬɨɱɧɢɤɨɦ ɢɧɮɨɪɦɚɰɢɢ ɨ ɪɟɝɟɧɟɪɚɬɢɜɧɨɦ ɩɨɬɟɧɰɢɚɥɟ ɨɪɝɚɧɢɡɦɚ.
103
Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɢɡɭɱɟɧɢɟ ɩɪɨɬɟɨɦɧɵɯ ɩɪɨɮɢɥɟɣ ɤɚɤ ɜɧɭɬɪɟɧɧɢɯ
ɫɬɟɧɨɤ ɫɨɫɭɞɨɜ, ɬɚɤ ɢ ȽɋɄ ɫɩɨɫɨɛɧɨ ɩɪɢɜɟɫɬɢ, ɜ ɩɟɪɫɩɟɤɬɢɜɟ, ɤ ɰɟɥɟɧɚɩɪɚɜɥɟɧɧɨɣ ɩɪɨɮɢɥɚɤɬɢɤɟ ɢ ɬɟɪɚɩɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɫ ɩɨɦɨɳɶɸ
ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ.
ɉɪɢ ɷɬɨɦ ɰɟɥɟɫɨɨɛɪɚɡɧɨ, ɜɢɞɢɦɨ, ɩɪɢɧɹɬɶ ɜɨ ɜɧɢɦɚɧɢɟ ɫɟɤɪɟɬɨɪɧɵɟ ɮɚɤɬɨɪɵ, ɫɩɨɫɨɛɧɵɟ ɩɨɜɥɹɬɶ ɧɚ ɪɚɡɜɢɬɢɟ ɢ ɜɵɠɢɜɚɧɢɟ ɋɄ. ɋɟɤɪɟɬɢɪɭɟɦɵɟ ɛɟɥɤɢ, ɤɚɤ ɢɡɜɟɫɬɧɨ, ɨɩɪɟɞɟɥɹɸɬ ɜ ɡɧɚɱɢɬɟɥɶɧɨɣ ɫɬɟɩɟɧɢ
ɝɨɦɟɨɫɬɚɡ ɢ ɤɨɦɦɭɧɢɤɚɰɢɢ ɜɧɭɬɪɢ ɤɚɪɞɢɨɜɚɫɤɭɥɹɪɧɨɣ ɫɢɫɬɟɦɵ ɜ ɨɬɜɟɬ ɧɚ ɟɟ ɩɨɪɚɠɟɧɢɟ. ȼɚɠɧɭɸ ɪɨɥɶ ɢɝɪɚɸɬ ɢ ɩɨɜɟɪɯɧɨɫɬɧɵɟ ɛɟɥɤɢ ɋɄ.
ɂɫɫɥɟɞɨɜɚɧɢɟ ɩɪɨɬɟɨɦɚ ɷɥɟɦɟɧɬɨɜ ɋɋɋ, ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɟ
ɢɡɦɟɧɟɧɢɹ ɜ ɤɨɬɨɪɨɣ ɡɚɬɪɚɝɢɜɚɸɬ ɦɧɨɝɢɟ ɟɟ ɤɨɦɩɨɧɟɧɬɵ, ɜɤɥɸɱɚɹ
ɝɥɚɞɤɨɦɵɲɟɱɧɵɟ ɢ ɷɧɞɨɬɟɥɢɚɥɶɧɵɟ ɤɥɟɬɤɢ, ɭɠɟ ɩɪɢɜɥɟɤɚɟɬ ɜɧɢɦɚɧɢɟ
ɪɹɞɚ ɭɱɟɧɵɯ. Ⱥɜɬɨɪɵ ɷɬɢɯ ɪɚɛɨɬ ɩɨɥɚɝɚɸɬ, ɱɬɨ ɜɵɹɜɥɟɧɢɟ ɦɨɞɢɮɢɰɢɪɭɟɦɵɯ ɩɚɬɨɥɨɝɢɟɣ ɛɟɥɤɨɜ ɦɨɠɟɬ ɞɚɬɶ ɤɥɸɱ ɤɚɤ ɤ ɩɨɧɢɦɚɧɢɸ ɦɟɯɚɧɢɡɦɨɜ ɚɬɟɪɨɫɤɥɟɪɡɚ, ɬɚɤ ɢ ɤ ɟɝɨ ɥɟɱɟɧɢɸ. ȼ ɞɚɧɧɵɣ ɦɨɦɟɧɬ ɬɚɤɢɯ
ɷɤɫɩɟɪɢɦɟɧɬɨɜ, ɯɚɪɚɤɬɟɪɢɡɭɟɦɵɯ ɤɚɤ «ɮɭɧɤɰɢɨɧɚɥɶɧɚɹ ɩɪɨɬɟɨɦɢɤɚ»,
ɜɵɩɨɥɧɟɧɨ ɹɜɧɨ ɧɟɞɨɫɬɚɬɨɱɧɨ. Ɍɟɦ ɧɟ ɦɟɧɟɟ, ɫɨɨɬɜɟɬɫɬɜɭɸɳɟɟ ɩɨɜɟɞɟɧɢɟ ɛɟɥɤɨɜ, ɜɤɥɸɱɚɹ ɢɡɦɟɧɟɧɢɟ ɢɯ ɤɨɥɢɱɟɫɬɜɚ, ɢɡɭɱɚɥɨɫɶ ɩɪɢ ɤɚɪɞɢɨɦɢɨɩɚɬɢɹɯ ɱɟɥɨɜɟɤɚ ɢ ɠɢɜɨɬɧɵɯ ɢ ɜ ɪɹɞɟ ɞɪɭɝɢɯ ɫɥɭɱɚɟɜ. ɋɨɝɥɚɫɧɨ
ɩɪɟɞɜɚɪɢɬɟɥɶɧɵɦ ɞɚɧɧɵɦ, ɧɚɢɛɨɥɟɟ ɨɛɟɳɚɸɳɢɦɢ ɦɚɪɤɟɪɚɦɢ ɞɥɹ ɤɚɪɞɢɨɩɪɨɬɟɨɦɢɤɢ
ɦɨɝɭɬ
ɛɵɬɶ
ɬɪɨɩɨɧɢɧɵ,
ɢɡɨɮɨɪɦɵ
ɚɥɶɮɚ-1-
ɮɢɛɪɢɧɨɝɟɧɚ, ɢɡɨɮɨɪɦɵ ɚɩɨɥɢɩɨɩɪɨɬɟɢɧɚ Ⱥ-1, ɋ-ɪɟɚɤɬɢɜɧɵɣ ɛɟɥɨɤ ɢ
ɞɪ. [1,10,16,30].
Ƚɥɚɜɧɨɟ ɩɪɟɩɹɬɫɬɜɢɟ ɞɥɹ ɚɧɚɥɢɡɚ ɩɪɨɬɟɨɦɚ ɫɨɫɭɞɨɜ ɩɪɢ ɚɬɟɪɨɝɟɧɟɡɟ – ɝɟɬɟɪɨɝɟɧɧɨɫɬɶ ɤɥɟɬɨɱɧɨɝɨ ɫɨɫɬɚɜɚ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɛɥɹɲɟɤ. Ⱦɪɭɝɨɣ ɦɟɬɨɞɢɱɟɫɤɨɣ ɩɪɨɛɥɟɦɨɣ ɹɜɥɹɟɬɫɹ ɜɵɛɨɪ ɚɞɟɤɜɚɬɧɨɝɨ
ɤɨɧɬɪɨɥɹ, ɫ ɚɤɰɟɧɬɨɦ ɧɚ ɥɨɤɚɥɢɡɚɰɢɸ ɨɛɪɚɡɰɨɜ ɜ ɫɨɫɭɞɢɫɬɨɣ ɫɬɟɧɤɟ ɢ
ɨɬɫɭɬɫɬɜɢɟ ɩɪɨɬɟɨɥɢɬɢɱɟɫɤɢɯ ɢɡɦɟɧɟɧɢɣ ɞɨ ɧɚɱɚɥɚ ɚɧɚɥɢɡɚ. ɋ ɭɱɟɬɨɦ
104
ɜɨɫɩɚɥɢɬɟɥɶɧɨɣ ɩɪɢɪɨɞɵ ɚɬɟɪɨɫɤɥɟɪɨɡɚ, ɫɥɟɞɭɟɬ ɩɪɢɧɢɦɚɬɶ ɜɨ ɜɧɢɦɚɧɢɟ ɬɚɤɠɟ ɜɡɚɢɦɨɞɟɣɫɬɜɢɟ ɦɟɠɞɭ ɢɧɮɢɥɶɬɪɨɜɚɧɧɵɦɢ Ɍ-ɥɢɦɮɨɰɢɬɚɦɢ ɢ
ɦɚɤɪɨɮɚɝɚɦɢ, ɨɛɪɚɡɨɜɚɧɧɵɦɢ ɢɡ ɦɨɧɨɰɢɬɨɜ. Ɇɚɤɪɨɮɚɝɢ ɞɨɜɨɥɶɧɨ
ɦɧɨɝɨɱɢɫɥɟɧɧɵ ɢ ɦɨɝɭɬ ɦɚɫɤɢɪɨɜɚɬɶ ɛɟɥɤɢ, ɩɪɨɢɫɯɨɞɹɳɢɟ ɢɡ ɤɨɦɩɨɧɟɧɬɨɜ ɧɨɪɦɚɥɶɧɨɣ ɫɬɟɧɤɢ ɫɨɫɭɞɨɜ. Ȼɨɥɟɟ ɬɨɝɨ, ɨɛɧɚɪɭɠɟɧɧɨɟ ɭɜɟɥɢɱɟɧɢɟ ɤɨɥɢɱɟɫɬɜɚ ɤɚɤɨɝɨ-ɥɢɛɨ ɛɟɥɤɚ ɦɨɠɟɬ ɹɜɥɹɬɶɫɹ ɪɟɡɭɥɶɬɚɬɨɦ ɢɧɮɢɥɶɬɪɚɰɢɢ ɦɨɧɨɰɢɬɨɜ ɜ ɩɨɪɚɠɟɧɧɭɸ ɚɪɬɟɪɢɸ.
ɇɟɫɦɨɬɪɹ ɧɚ ɷɬɢ ɨɝɪɚɧɢɱɟɧɢɹ, ɩɟɪɜɵɟ ɩɨɩɵɬɤɢ ɚɧɚɥɢɡɚ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ ɩɨɪɚɠɟɧɢɹ ɫ ɩɨɦɨɳɶɸ 2-D ɛɵɥɢ ɩɪɟɞɩɪɢɧɹɬɵ ɩɨɱɬɢ
20 ɥɟɬ ɧɚɡɚɞ. Ɍɚɤ, Stastny et al. [81] ɫɪɚɜɧɢɜɚɥ ɛɟɥɤɨɜɵɣ ɫɨɫɬɚɜ ɥɢɩɨɮɢɛɪɨɡɧɨɣ ɛɥɹɲɤɢ ɫ ɫɨɫɬɚɜɨɦ ɧɨɪɦɚɥɶɧɨɣ ɢɧɬɢɦɵ ɢ ɨɛɧɚɪɭɠɢɥ, ɱɬɨ
ɛɟɥɤɢ ɩɥɚɡɦɟɧɧɨɝɨ ɩɪɨɢɫɯɨɠɞɟɧɢɹ (ɚɥɶɛɭɦɢɧ, ɮɢɛɪɢɧɨɝɟɧ, ɢɦɦɭɧɨɝɥɨɛɭɥɢɧ G, a-1 ɚɧɬɢɬɪɢɩɫɢɧ, ɬɪɚɧɫɮɟɪɪɢɧ, ɝɚɩɬɨɝɥɨɛɢɧ, Ⱥɩo A-I, and
Ⱥɩo A-II) ɚɤɤɭɦɭɥɢɪɭɸɬɫɹ ɜ ɩɨɪɚɠɟɧɧɵɯ ɫɨɫɭɞɚɯ. Ⱥɧɚɥɨɝɢɱɧɨ, Song
et al. [79] ɨɛɧɚɪɭɠɢɥ, ɱɬɨ ɛɟɥɤɢ ɢɡ ɩɥɚɡɦɵ ɫɬɚɧɨɜɹɬɫɹ ɛɨɥɟɟ ɦɧɨɝɨɱɢɫɥɟɧɧɵ ɜ ɢɧɬɢɦɟ ɚɪɬɟɪɢɣ ɩɪɢ ɫɬɚɪɟɧɢɢ ɨɞɧɨɜɪɟɦɟɧɧɨ ɫ ɭɬɨɥɳɟɧɢɟɦ ɢɧɬɢɦɵ.
ɍɫɬɚɧɨɜɥɟɧɨ, ɱɬɨ ɨɫɬɟɨɧɟɤɬɢɧ ɭɫɢɥɟɧɧɨ ɷɤɫɩɪɟɫɫɢɪɭɟɬɫɹ ɤɥɟɬɤɚɦɢ, ɩɪɢɫɭɬɫɬɜɭɸɳɢɦɢ ɜ ɫɬɟɧɤɟ ɫɨɫɭɞɚ ɩɪɢ ɩɪɨɝɪɟɫɫɢɪɨɜɚɧɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ, ɚ ɢɦɟɧɧɨ ɩɪɢ ɤɚɥɶɰɢɮɢɤɚɰɢɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɣ
ɛɥɹɲɤɢ [28].
ȼ ɛɨɥɟɟ ɩɨɡɞɧɢɯ ɪɚɛɨɬɚɯ ɫ ɩɨɦɨɳɶɸ ɥɚɡɟɪɧɨɣ ɞɟɧɫɢɬɨɦɟɬɪɢɢ
ɛɵɥɨ ɩɨɞɬɜɟɪɠɞɟɧɨ ɡɧɚɱɢɬɟɥɶɧɨɟ ɭɜɟɥɢɱɟɧɢɟ ɨɬɧɨɲɟɧɢɹ ɚɥɶɛɭɦɢɧ/ɚɤɬɢɧ ɜ ɠɢɪɨɜɵɯ ɩɨɥɨɫɚɯ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɧɨɪɦɨɣ [83]. ɉɪɢ ɫɪɚɜɧɟɧɢɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɛɥɹɲɟɤ ɤɨɪɨɧɚɪɧɵɯ ɚɪɬɟɪɢɣ ɫ ɧɨɪɦɚɥɶɧɵɦɢ ɤɨɪɨɧɚɪɧɵɦɢ ɚɪɬɟɪɢɹɦɢ You ɩɪɨɞɟɦɨɧɫɬɪɢɪɨɜɚɥ ɭɜɟɥɢɱɟɧɢɟ
ɷɤɫɩɪɟɫɫɢɢ ɮɟɪɪɢɬɢɧɚ (ɛɟɥɤɚ, ɭɱɚɫɬɜɭɸɳɟɝɨ ɜ ɤɥɟɬɨɱɧɨɦ ɧɚɤɨɩɥɟɧɢɢ
ɠɟɥɟɡɚ) ɜ ɤɨɪɨɧɚɪɧɵɯ ɚɪɬɟɪɢɹɯ ɢɧɞɢɜɢɞɨɜ ɫ ɡɚɛɨɥɟɜɚɧɢɹɦɢ ɤɨɪɨɧɚɪ105
ɧɵɯ ɚɪɬɟɪɢɣ [104]. ȼ ɝɨɦɨɝɟɧɚɬɚɯ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɯ ɛɥɹɲɟɤ ɱɟɥɨɜɟɤɚ ɨɛɧɚɪɭɠɟɧɨ 2-ɤɪɚɬɧɨɟ ɭɜɟɥɢɱɟɧɢɟ ɥɟɝɤɨɰɟɩɨɱɟɱɧɨɝɨ ɮɟɪɪɢɬɢɧɚ
ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɤɨɧɬɪɨɥɟɦ. ɉɪɟɞɩɨɥɚɝɚɟɬɫɹ ɭɱɚɫɬɢɟ ɷɬɨɝɨ ɛɟɥɤɚ ɜ ɨɛɪɚɡɨɜɚɧɢɢ ɚɤɬɢɜɧɵɯ ɮɨɪɦ ɤɢɫɥɨɪɨɞɚ, ɜɵɡɵɜɚɸɳɢɯ ɨɤɢɫɥɟɧɢɟ ɥɢɩɢɞɨɜ ɜ ɫɬɟɧɤɟ ɤɨɪɨɧɚɪɧɵɯ ɚɪɬɟɪɢɣ.
ȼ ɧɟɫɬɚɛɢɥɶɧɵɯ ɛɥɹɲɤɚɯ (ɩɨɫɥɟɞɧɢɟ ɫɬɚɞɢɢ ɪɚɡɜɢɬɢɹ) ɨɛɧɚɪɭɠɟɧɵ ɬɚɤɠɟ ɢɡɨɮɨɪɦɵ Į1-ɚɧɬɢɬɪɢɩɫɢɧɚ [55] ɢ ɧɚɛɨɪɚ ɢɡ 27 ɛɟɥɤɨɜ, ɭɱɚɫɬɜɭɸɳɢɯ ɜ ɛɢɨɥɨɝɢɱɟɫɤɢɯ ɩɪɨɰɟɫɫɚɯ (ɦɢɝɪɚɰɢɢ ɝɥɚɞɤɨɦɵɲɟɱɧɵɯ
ɤɥɟɬɨɤ, ɚɤɬɢɜɚɰɢɢ ɦɟɬɚɥɥɨɩɪɨɬɟɢɧɚɡ ɦɚɬɪɢɤɫɚ, ɪɟɝɭɥɹɰɢɢ ɩɪɨɜɨɫɩɚɥɢɬɟɥɶɧɵɯ ɰɢɬɨɤɢɧɨɜ).
ȼ ɨɬɥɢɱɢɟ ɨɬ ɜɵɹɫɧɟɧɢɹ ɪɨɥɢ ɨɬɞɟɥɶɧɵɯ ɛɟɥɤɨɜ ɜ ɪɚɡɜɢɬɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ, ɩɪɨɬɟɨɦɢɤɚ ɩɨɡɜɨɥɹɟɬ ɨɰɟɧɢɬɶ ɦɢɤɪɨɨɤɪɭɠɟɧɢɟ ɛɥɹɲɤɢ ɜ
ɰɟɥɨɦ. Ɍɚɤ, ɨɛɧɚɪɭɠɟɧɨ ɫɧɢɠɟɧɢɟ ɛɟɥɤɚ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ (hsp27) ɜ ɫɭɩɟɪɧɚɬɚɧɬɟ ɤɭɥɶɬɭɪɵ ɩɨɪɚɠɟɧɧɵɯ ɚɬɟɪɨɫɤɥɟɪɨɡɨɦ ɤɥɟɬɨɤ, ɚ ɬɚɤɠɟ
hsp27, hsp20, ɫɭɩɟɪɨɤɫɢɞɞɢɫɦɭɬɚɡɵ 3 ɜ ɫɬɚɛɢɥɶɧɵɯ ɛɥɹɲɤɚɯ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ ɧɟɫɬɚɛɢɥɶɧɵɦɢ [63].
ɇɚɤɨɧɟɰ, ɫɥɟɞɭɟɬ ɭɤɚɡɚɬɶ ɧɚ ɪɚɛɨɬɭ, ɜ ɤɨɬɨɪɨɣ ɢɡɭɱɚɥɢɫɶ ɛɟɥɤɢ
ɢɡ ɢɦɦɭɧɨɝɢɫɬɨɯɢɦɢɱɟɫɤɢ ɤɥɚɫɫɢɮɢɰɢɪɨɜɚɧɧɵɯ ɫɬɚɛɢɥɶɧɵɯ ɢ ɧɟɫɬɚɛɢɥɶɧɵɯ ɛɥɹɲɟɤ ɫɨɧɧɵɯ ɚɪɬɟɪɢɣ [60]. Ⱥɜɬɨɪɵ ɨɛɧɚɪɭɠɢɥɢ, ɱɬɨ ɨɤɨɥɨ
70% ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɯ ɛɟɥɤɨɜ ɩɪɨɢɫɯɨɞɹɬ ɢɡ ɩɥɚɡɦɵ, ɱɬɨ ɫɜɢɞɟɬɟɥɶɫɬɜɭɟɬ ɨ ɧɚɪɭɲɟɧɢɢ ɛɚɪɶɟɪɧɵɯ ɮɭɧɤɰɢɣ ɷɧɞɨɬɟɥɢɹ ɧɟɡɚɜɢɫɢɦɨ ɨɬ
ɬɢɩɚ ɛɥɹɲɤɢ. ȼ ɧɟɫɬɚɛɢɥɶɧɵɯ ɛɥɹɲɤɚɯ, ɩɨ ɫɪɚɜɧɟɧɢɸ ɫɨ ɫɬɚɛɢɥɶɧɵɦɢ, ɫɧɢɠɚɥɨɫɶ ɫɨɞɟɪɠɚɧɢɟ ɫɭɩɟɪɨɤɫɢɞɞɢɫɦɭɬɚɡɵ 3 (ɋɈȾ 3) ɢ ɝɥɸɬɚɬɢɨɧ s-ɬɪɚɧɫɮɟɪɚɡɵ (ȽɋɌ), ɛɟɥɤɨɜ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ 20 ɢ 27, ɚɧɧɟɤɫɢɧɚ
Ⱥ10, ɚ ɜɨɡɪɚɫɬɚɥɨ ɫɨɞɟɪɠɚɧɢɟ ɥɟɝɤɨɝɨ ɮɟɪɪɢɬɢɧɚ, ɋɈȾ 2 ɢ ɮɪɚɝɦɟɧɬɚ
D ɮɢɛɪɢɧɨɝɟɧɚ. Ʉɚɤ ɢɡɜɟɫɬɧɨ, ɜɫɟ ɷɬɢ ɛɟɥɤɢ ɬɚɤ ɢɥɢ ɢɧɚɱɟ ɜɨɜɥɟɱɟɧɵ
ɜ ɨɤɢɫɥɢɬɟɥɶɧɵɟ ɢɥɢ ɜɨɫɩɚɥɢɬɟɥɶɧɵɟ ɩɪɨɰɟɫɫɵ, ɚ ɬɚɤɠɟ ɨɛɪɚɡɨɜɚɧɢɟ
ɛɥɹɲɟɤ.
106
Ⱥɥɶɬɟɪɧɚɬɢɜɧɵɣ ɩɨɞɯɨɞ ɤ ɢɫɫɥɟɞɨɜɚɧɢɸ ɩɪɨɬɟɨɦɚ ɛɥɹɲɤɢ ɩɪɢɦɟɧɢɥ Duran and Mas et al. [29]. ȼ ɷɬɢɯ ɨɩɵɬɚɯ ɨɛɪɚɡɰɵ ɢɡ ɫɨɧɧɵɯ ɚɪɬɟɪɢɣ
ɤɭɥɶɬɢɜɢɪɨɜɚɥɢ ɜ ɛɟɡɛɟɥɤɨɜɨɣ ɫɪɟɞɟ ɢ ɚɧɚɥɢɡɢɪɨɜɚɥɢ ɫɭɩɟɪɧɚɬɚɧɬ ɫ ɩɨɦɨɳɶɸ 2-DE. ɍɫɬɚɧɨɜɥɟɧɨ, ɱɬɨ ɛɟɥɤɢ, ɜɵɫɜɨɛɨɠɞɚɟɦɵɟ ɢɡ ɛɥɹɲɟɤ, ɜɨɜɥɟɱɟɧɵ ɜ ɨɛɪɚɬɧɵɣ ɬɪɚɧɫɩɨɪɬ ɯɨɥɟɫɬɟɪɢɧɚ (ɚɩɨɥɢɩɨɩɪɨɬɟɢɧ ȼ-100,
ɚɩɨɥɢɩɨɩɪɨɬɟɢɧ Ⱥ-1), ɚɩɨɩɬɨɡ (ɥɟɤɬɢɧ, ɪɚɫɬɜɨɪɹɟɦɵɣ b-ɝɚɥɚɤɬɨɡɢɞɚɡɨɣ),
ɞɟɝɪɚɞɚɰɢɸ ɛɟɥɤɨɜ (ɝɢɞɪɨɥɚɡɚ 23) ɢ ɚɧɬɢɨɤɢɫɥɢɬɟɥɶɧɨɟ ɞɟɣɫɬɜɢɟ (ɫɭɩɟɪɨɤɫɢɞɞɢɫɦɭɬɚɡɚ, ɩɟɪɨɤɫɢɪɟɞɨɤɫɢɧ 2). ɋ ɩɨɜɵɲɟɧɢɟɦ ɫɥɨɠɧɨɫɬɢ ɩɨɪɚɠɟɧɢɹ ɜɨɡɪɚɫɬɚɥɨ ɢ ɤɨɥɢɱɟɫɬɜɨ ɛɟɥɤɨɜ. Ɉɞɧɚɤɨ ɧɟɹɫɧɨ, ɜɵɞɟɥɹɸɬɫɹ
ɥɢ ɷɬɢ ɛɟɥɤɢ ɢɡ ɛɥɹɲɟɤ ɚɤɬɢɜɧɨ ɢɥɢ ɩɚɫɫɢɜɧɚɹ ɞɢɮɮɭɡɢɹ ɜ ɫɪɟɞɭ ɤɥɟɬɨɱɧɨɣ ɤɭɥɶɬɭɪɵ ɩɪɨɢɫɯɨɞɢɬ ɥɟɝɱɟ ɢɡ ɛɥɹɲɟɤ, ɱɟɦ ɢɡ ɧɨɪɦɚɥɶɧɵɯ ɚɪɬɟɪɢɣ. Ȼɟɥɨɤ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ 27, ɫɟɤɪɟɬɢɪɭɟɦɵɣ ɢɡ ɛɥɹɲɤɢ ɜ ɤɭɥɶɬɭɪɚɥɶɧɭɸ ɫɪɟɞɭ, ɪɚɫɫɦɚɬɪɢɜɚɟɬɫɹ ɤɚɤ ɩɨɬɟɧɰɢɚɥɶɧɵɣ ɦɚɪɤɟɪ ɚɬɟɪɨɫɤɥɟɪɨɡɚ, ɩɨɫɤɨɥɶɤɭ ɟɝɨ ɫɨɞɟɪɠɚɧɢɟ ɫɧɢɠɚɟɬɫɹ ɤɚɤ ɩɨ ɫɪɚɜɧɟɧɢɸ ɫ
ɤɨɧɬɪɨɥɟɦ in vitro, ɬɚɤ ɢ ɜ ɩɥɚɡɦɟ ɤɪɨɜɢ in vivo. Ⱦɪɭɝɢɦ ɦɚɪɤɟɪɨɦ ɜ
ɪɚɛɨɬɚɯ ɷɬɨɣ ɠɟ ɝɪɭɩɩɵ ɢɫɫɥɟɞɨɜɚɬɟɥɟɣ ɩɪɢɡɧɚɟɬɫɹ ɤɚɬɟɩɫɢɧ D.
ɉɪɢɧɰɢɩɢɚɥɶɧɨ ɧɨɜɭɸ ɦɟɬɨɞɢɤɭ ɢɫɫɥɟɞɨɜɚɧɢɹ ɩɪɨɬɟɨɦɧɨɝɨ
ɩɪɨɮɢɥɹ ɛɥɹɲɤɢ ɩɪɟɞɥɨɠɢɥɚ ɝɪɭɩɩɚ David Han [11], ɪɚɡɪɚɛɨɬɚɜɲɚɹ
ɬ.ɧ. ɩɪɨɰɟɞɭɪɭ ɩɪɹɦɨɣ ɬɤɚɧɟɜɨɣ ɩɪɨɬɟɨɦɢɤɢ (DTP), ɩɨɡɜɨɥɹɸɳɭɸ
ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɬɶ ɛɟɥɤɢ ɜ ɦɢɧɢɦɚɥɶɧɵɯ ɤɨɥɢɱɟɫɬɜɚɯ ɬɤɚɧɢ ɫɨɫɭɞɚ. ɋ
ɷɬɨɣ ɰɟɥɶɸ ɛɟɥɤɢ ɷɤɫɬɪɚɝɢɪɭɸɬɫɹ ɢɡ ɮɢɤɫɢɪɨɜɚɧɧɵɯ ɮɨɪɦɚɥɶɞɟɝɢɞɨɦ
ɢ ɩɨɝɪɭɠɟɧɧɵɯ ɜ ɩɚɪɚɮɢɧ ɨɛɪɚɡɰɨɜ ɬɤɚɧɢ, ɱɬɨ ɨɛɟɫɩɟɱɢɜɚɟɬ ɢɯ ɛɨɥɟɟ
ɷɮɮɟɤɬɢɜɧɨɟ ɪɚɡɞɟɥɟɧɢɟ. ɉɨɥɭɱɟɧɧɵɣ ɩɪɨɮɢɥɶ ɛɥɹɲɤɢ ɢɡ ɤɨɪɨɧɚɪɧɨɣ ɚɪɬɟɪɢɢ ɜɤɥɸɱɚɥ ɜ ɫɟɛɹ 806 ɛɟɥɤɨɜ, ɪɹɞ ɢɡ ɤɨɬɨɪɵɯ ɢ ɪɚɧɟɟ ɫɜɹɡɵɜɚɥɢ ɫ ɪɚɡɜɢɬɢɟɦ ɚɬɟɪɨɫɤɥɟɪɨɡɚ.
Ɉɞɧɚɤɨ, ɧɚɪɹɞɭ ɫ ɧɢɦɢ, ɛɵɥɢ ɨɛɧɚɪɭɠɟɧɵ ɜɵɩɨɥɧɹɸɳɢɟ ɪɟɝɭɥɹɬɨɪɧɵɟ ɮɭɧɤɰɢɢ PEDF (pigment-epithelium derived factor), ɩɟɪɢɨɫɬɢɧ
(periostin), MFG-E8 (milk fat globule-EGF-factor 8) ɢ aɧɧɟɤɫɢɧ I, ɚ ɬɚɤ107
ɠɟ ɧɟɤɨɬɨɪɵɟ ɮɚɤɬɨɪɵ ɪɨɫɬɚ ɢ ɰɢɬɨɤɢɧɵ. Ⱥɜɬɨɪɵ ɩɨɥɚɝɚɸɬ, ɱɬɨ ɢɦɢ ɜ
ɨɫɧɨɜɧɨɦ ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɵ ɛɟɥɤɢ ɜɧɟɤɥɟɬɨɱɧɨɝɨ ɦɚɬɪɢɤɫɚ, ɜɨɜɥɟɱɟɧɧɵɟ ɜ ɪɚɡɜɢɬɢɟ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɢ ɫɩɨɫɨɛɧɵɟ ɦɢɝɪɢɪɨɜɚɬɶ ɢɡ ɦɟɞɢɢ ɜ
ɢɧɬɢɦɭ.
Ʉɚɤ ɜ ɧɚɲɟɣ ɪɚɛɨɬɟ (ɚɤɰɟɧɬ ɧɚ ɢɫɫɥɟɞɨɜɚɧɢɢ ɬɚɤɢɯ ɫɬɪɭɤɬɭɪ, ɤɚɤ
ɢɧɬɢɦɚ ɢ ɦɟɞɢɹ), ɜɧɢɦɚɧɢɟ ɢɫɫɥɟɞɨɜɚɬɟɥɟɣ ɩɪɢɜɥɟɤɚɸɬ ɝɥɚɞɤɨɦɵɲɟɱɧɵɟ ɤɥɟɬɤɢ ɫɨɫɭɞɨɜ (ȽɆɄ), ɱɶɹ ɩɪɨɥɢɮɟɪɚɰɢɹ ɢ ɦɢɝɪɚɰɢɹ ɜɚɠɧɵ
ɞɥɹ ɪɚɡɜɢɬɢɹ ɩɚɬɨɥɨɝɢɢ. Ⱦɢɮɮɟɪɟɧɰɢɚɥɶɧɚɹ ɩɪɨɬɟɨɦɢɤɚ ɜɵɹɜɢɥɚ
ɜɚɠɧɭɸ ɪɨɥɶ ɯɚɩɟɪɨɧɨɜ, ɚ ɬɚɤɠɟ ɛɟɥɤɨɜ ɰɢɬɨɫɤɟɥɟɬɚ (ɜɢɦɟɧɬɢɧɚ ɢ ɚɤɬɢɧɚ) ɜ ɮɨɪɦɢɪɨɜɚɧɢɢ ɛɥɹɲɤɢ, ɩɪɨɞɨɥɠɚɟɬɫɹ ɢɡɭɱɟɧɢɟ ɜɥɢɹɧɢɹ ɧɚ
ȽɆɄ ɨɤɢɫɥɟɧɧɵɯ Ʌɉɇɉ, ɨɤɢɫɥɢɬɟɥɶɧɨɝɨ ɫɬɪɟɫɫɚ, ɦɟɯɚɧɢɱɟɫɤɨɝɨ ɝɟɧɨɞɢɧɚɦɢɱɟɫɤɨɝɨ ɧɚɩɪɹɠɟɧɢɹ. ȼ ɱɚɫɬɧɨɫɬɢ, ɜ ɩɨɫɥɟɞɧɟɦ ɫɥɭɱɚɟ ɨɛɧɚɪɭɠɟɧɨ ɢɡɦɟɧɟɧɢɟ ɭɪɨɜɧɟɣ ɝɟɥɫɨɥɢɧɚ, hsp27 ɢ ɋɚɪZ [64]. Ɂɞɟɫɶ ɭɦɟɫɬɧɨ ɨɬɦɟɬɢɬɶ, ɱɬɨ ɢ ɞɪɭɝɢɟ ɚɜɬɨɪɵ ɨɛɧɚɪɭɠɢɥɢ ɭɜɟɥɢɱɟɧɢɟ ɷɤɫɩɪɟɫɫɢɢ
hsp60 ɢ hsp70 ɩɪɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɦ ɩɨɪɚɠɟɧɢɢ [98].
ɋ ɭɱɟɬɨɦ ɩɪɟɞɫɬɚɜɥɟɧɧɵɯ ɡɞɟɫɶ ɪɟɡɭɥɶɬɚɬɨɜ ɢɫɫɥɟɞɨɜɚɧɢɣ, ɫɯɨɞɧɵɯ ɫ ɜɵɩɨɥɧɟɧɧɵɦɢ ɧɚɦɢ, ɫɥɟɞɭɟɬ ɭɤɚɡɚɬɶ, ɤɚɤ ɦɢɧɢɦɭɦ, ɧɚ ɩɨɞɬɜɟɪɠɞɟɧɢɟ ɪɨɥɢ ɜ ɮɨɪɦɢɪɨɜɚɧɢɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɣ ɛɥɹɲɤɢ ɬɚɤɢɯ
ɧɢɡɤɨɦɨɥɟɤɭɥɹɪɧɵɯ ɛɟɥɤɨɜ, ɤɚɤ ɚɧɧɟɤɫɢɧɵ ɢ ɛɟɥɤɢ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ.
ɉɪɢ ɷɬɨɦ ɭɦɟɫɬɧɨ ɫɧɨɜɚ ɭɤɚɡɚɬɶ ɧɚ ɪɚɛɨɬɭ Tao ɫ ɫɨɬɪɭɞɧɢɤɚɦɢ
[86], ɤɨɬɨɪɵɣ ɨɛɧɚɪɭɠɢɥ, ɱɬɨ ɛɟɥɤɢ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ (ɢ ɯɚɩɟɪɨɧɵ) ɞɨɦɢɧɢɪɭɸɬ ɜ CD34+ ɤɥɟɬɤɚɯ.
Ɍɟɦ ɧɟ ɦɟɧɟɟ, ɫɨɜɟɪɲɟɧɧɨ ɹɫɧɨ, ɱɬɨ ɞɥɹ ɭɬɨɱɧɟɧɢɹ ɪɨɥɢ ɛɟɥɤɨɜ ɜ
ɚɬɟɪɨɝɟɧɟɡɟ ɫ ɩɨɦɨɳɶɸ ɩɪɨɬɟɨɦɢɤɢ ɧɟɨɛɯɨɞɢɦɵ ɞɚɥɶɧɟɣɲɢɟ ɢɫɫɥɟɞɨɜɚɧɢɹ ɧɚ ɜɵɪɟɡɚɟɦɵɯ ɥɚɡɟɪɨɦ ɦɢɤɪɨɭɱɚɫɬɤɚɯ ɫɨɫɭɞɨɜ, ɚ ɬɚɤɠɟ
ɨɰɟɧɤɚ ɩɨɫɬɬɪɚɧɫɥɹɰɢɨɧɧɵɯ ɦɨɞɢɮɢɤɚɰɢɣ ɛɟɥɤɨɜ, ɜ ɱɚɫɬɧɨɫɬɢ, ɨɤɢɫɥɢɬɟɥɶɧɨɝɨ ɯɚɪɚɤɬɟɪɚ, ɱɬɨ ɦɨɠɟɬ ɛɵɬɶ ɩɨɥɟɡɧɵɦ ɤɚɤ ɞɥɹ ɨɛɧɚɪɭɠɟɧɢɹ
ɧɨɜɵɯ ɦɚɪɤɟɪɨɜ ɩɚɬɨɥɨɝɢɢ, ɬɚɤ ɢ ɞɥɹ ɰɟɥɟɣ ɬɟɪɚɩɢɢ.
108
ȼ ɬɨ ɠɟ ɜɪɟɦɹ ɩɨɤɚ ɜɟɫɶɦɚ ɫɨɦɧɢɬɟɥɶɧɨ, ɱɬɨ ɩɪɨɮɢɥɚɤɬɢɤɚ ɢ ɥɟɱɟɧɢɟ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɫ ɩɨɦɨɳɶɸ ȽɋɄ – ɞɨɫɬɚɬɨɱɧɨ ɛɥɢɡɤɚɹ ɩɟɪɫɩɟɤɬɢɜɚ. ɋ ɨɞɧɨɣ ɫɬɨɪɨɧɵ, ɟɳɟ ɜ 2001 ɝ. ɛɵɥɨ ɩɪɨɞɟɦɨɧɫɬɪɢɪɨɜɚɧɨ, ɱɬɨ
ɜɧɭɬɪɢɜɟɧɧɨɟ ɜɜɟɞɟɧɢɟ CD34+ ɤɥɟɬɨɤ ɜɟɞɟɬ ɤ ɭɥɭɱɲɟɧɢɸ ɮɭɧɤɰɢɨɧɢɪɨɜɚɧɢɹ ɋɋɋ [50]. ɋ ɞɪɭɝɨɣ ɫɬɨɪɨɧɵ, ɦɟɯɚɧɢɡɦɵ, ɩɨɫɪɟɞɫɬɜɨɦ ɤɨɬɨɪɵɯ ɬɪɚɧɫɩɥɚɧɬɢɪɨɜɚɧɧɵɟ ɋɄ ɜɥɢɹɸɬ ɧɚ ɫɨɫɭɞɵ, ɨɫɬɚɸɫɹ ɦɚɥɨɩɨɧɹɬɧɵɦɢ. ȼɨɡɦɨɠɧɨ, ɋɄ ɞɢɮɮɟɪɟɧɰɢɪɭɸɬɫɹ ɜ ɤɥɟɬɤɢ, ɫɩɨɫɨɛɧɵɟ ɤ
ɡɚɦɟɳɟɧɢɸ ɫɬɪɭɤɬɭɪ, ɩɨɪɚɠɟɧɧɵɯ ɜ ɩɪɨɰɟɫɫɟ ɚɬɟɪɨɝɟɧɟɡɚ (ɧɟɨɚɧɝɢɨɝɟɧɟɡ). ȼɦɟɫɬɨ ɩɪɹɦɵɯ ɞɨɤɚɡɚɬɟɥɶɫɬɜ ɬɚɤɨɣ ɜɨɡɦɨɠɧɨɫɬɢ ɫɭɳɟɫɬɜɭɸɬ
ɩɪɟɞɩɨɥɨɠɟɧɢɹ ɨ ɦɟɯɚɧɢɡɦɚɯ ɢ ɮɚɤɬɨɪɚɯ, ɦɨɞɭɥɢɪɭɸɳɢɯ ɤɥɟɬɨɱɧɨɟ
ɞɟɥɟɧɢɟ, ɚɩɨɩɬɨɡ, ɝɨɦɟɨɫɬɚɡ ɢ ɬ.ɩ. ɉɪɢ ɷɬɨɦ ɛɨɥɟɟ ɢɡɭɱɟɧɧɵɦɢ ɹɜɥɹɸɬɫɹ ɷɦɛɪɢɨɧɚɥɶɧɵɟ ɋɄ, ɬɨɝɞɚ ɤɚɤ ɜɨɡɦɨɠɧɨɫɬɢ ȽɋɄ ɢɡɜɟɫɬɧɵ ɝɨɪɚɡɧɨ ɦɟɧɶɲɟ.
ȼ ɧɚɲɟɣ ɪɚɛɨɬɟ ɧɚɪɹɞɭ ɫ ȽɋɄ ɩɪɨɬɟɨɦɧɵɦ ɢɫɫɥɟɞɨɜɚɧɢɹɦ ɛɵɥɢ
ɩɨɞɜɟɪɝɧɭɬɵ ɨɫɬɟɨɛɥɚɫɬɵ ɢ ȽɆɄ ɚɪɬɟɪɢɣ. ɉɨɞɱɟɪɤɧɟɦ ɟɳɟ ɪɚɡ, ɱɬɨ
ɥɨɤɚɥɶɧɨɟ ɦɢɤɪɨɨɤɪɭɠɟɧɢɟ, ɜ ɤɨɬɨɪɨɟ ɜɯɨɞɹɬ ɨɫɬɟɨɛɥɚɫɬɵ ɢ ȽɆɄ,
ɨɩɪɟɞɟɥɹɟɬ ɤɚɤ ɧɚɩɪɚɜɥɟɧɢɟ ɞɢɮɮɟɪɟɧɰɢɚɰɢɢ ȽɋɄ, ɬɚɤ ɢ ɮɢɛɪɨɡ
ɢɧɬɢɦɵ ɫɬɟɧɤɢ ɫɨɫɭɞɨɜ, ɯɨɧɞɪɨ- ɢ ɨɫɬɟɨɝɟɧɟɡ ɫ ɩɨɫɥɟɞɭɸɳɟɣ ɤɚɥɶɰɢɮɢɤɚɰɢɟɣ. Ɍɚɤɢɦ ɨɛɪɚɡɨɦ, ɜɫɟ ɷɬɢ ɬɪɢ ɫɬɪɭɤɬɭɪɧɵɯ ɷɥɟɦɟɧɬɚ –
ɜɡɚɢɦɨɡɚɜɢɫɢɦɵ. Ⱥɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɟ ɩɨɪɚɠɟɧɢɹ ɫɨɞɟɪɠɚɬ ɨɫɬɟɨɛɥɚɫɬ-ɩɨɞɨɛɧɵɟ ɤɥɟɬɤɢ, ɭɥɶɬɪɚɫɬɪɭɤɬɭɪɚ ɤɨɬɨɪɵɯ ɧɚɩɨɦɢɧɚɟɬ ȽɆɄ.
ȼ ɬɨ ɠɟ ɜɪɟɦɹ ɩɪɟɞɩɨɥɚɝɚɟɬɫɹ, ɱɬɨ ɨɫɬɟɨɛɥɚɫɬɵ ɩɪɨɢɫɯɨɞɹɬ ɢɡ ɋɄ,
ɩɪɨɧɢɤɚɸɳɢɯ ɜ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɢɟ ɛɥɹɲɤɢ ɢɡ ɤɪɨɜɹɧɨɝɨ ɪɭɫɥɚ.
ȼɢɞɢɦɨ, ɫɥɟɞɭɸɳɢɣ ɲɚɝ ɞɥɹ ɩɨɧɢɦɚɧɢɹ ɩɪɨɰɟɫɫɨɜ ɚɬɟɪɨɝɟɧɟɡɚ ɢ
ɜɨɡɦɨɠɧɨɫɬɟɣ ȽɋɄ ɞɥɹ ɟɝɨ ɬɟɪɚɩɢɢ – ɨɞɧɨɜɪɟɦɟɧɧɨɟ ɧɚɛɥɸɞɟɧɢɟ ɫ
ɩɨɦɨɳɶɸ ɩɪɨɬɟɨɦɢɤɢ ɡɚ ɞɢɧɚɦɢɤɨɣ ɢɡɦɟɧɟɧɢɹ ɋɄ, ȽɆɄ ɢ ɨɫɬɟɨɛɥɚɫɬɨɜ ɩɪɢ ɪɚɡɜɢɬɢɢ ɷɬɨɣ ɩɚɬɨɥɨɝɢɢ.
109
110
ȼɕȼɈȾɕ
1.
Ɉɩɬɢɦɢɡɢɪɨɜɚɧ ɚɥɝɨɪɢɬɦ ɩɪɨɬɟɨɦɧɨɝɨ ɚɧɚɥɢɡɚ – ɫɨɡɞɚɧɚ
ɟɞɢɧɚɹ ɫɯɟɦɚ ɢɫɫɥɟɞɨɜɚɧɢɹ ɛɟɥɤɨɜɵɯ ɩɪɨɮɢɥɟɣ, ɭɩɪɨɳɚɸɳɚɹ ɫɪɚɜɧɟɧɢɟ ɞɚɧɧɵɯ, ɩɨɥɭɱɟɧɧɵɯ ɧɚ ɬɚɤɢɯ ɪɚɡɧɵɯ ɨɛɴɟɤɬɚɯ, ɤɚɤ ɨɫɬɟɨɛɥɚɫɬɵ,
ɦɨɧɨɧɭɤɥɟɚɪɧɵɟ ɤɥɟɬɤɢ, CD34+ȽɋɄ ɢ ɢɧɬɢɦɨ-ɦɟɞɢɚɥɶɧɵɣ ɫɥɨɣ ɚɨɪɬɵ
ɱɟɥɨɜɟɤɚ. ɍɫɨɜɟɪɲɟɧɫɬɜɨɜɚɧɧɵɣ ɦɟɬɨɞ – ɤɨɦɛɢɧɚɰɢɹ 2D-ɷɥɟɤɬɪɨɮɨɪɟɡɚ
ɫ ɮɪɚɤɰɢɨɧɢɪɨɜɚɧɢɟɦ ɤɥɟɬɨɱɧɵɯ ɨɪɝɚɧɟɥɥ ɩɨɡɜɨɥɹɟɬ ɧɟ ɬɨɥɶɤɨ ɩɪɨɜɟɫɬɢ ɩɪɨɬɟɨɦɧɵɣ ɚɧɚɥɢɡ ɤɥɟɬɨɤ, ɧɨ ɢ ɩɨɥɭɱɢɬɶ ɢɧɮɨɪɦɚɰɢɸ ɨ ɜɧɭɬɪɢɤɥɟɬɨɱɧɨɣ ɥɨɤɚɥɢɡɚɰɢɢ ɫɩɟɰɢɮɢɱɟɫɤɢɯ ɛɟɥɤɨɜ.
2.
ɂɡɭɱɟɧɨ ɫ ɩɨɦɨɳɶɸ ɩɪɨɬɟɨɦɢɤɢ ɩɨɜɟɞɟɧɢɟ ɛɟɥɤɨɜ ɨɫɬɟɨ-
ɛɥɚɫɬɨɜ, ɢɡɦɟɧɹɸɳɢɯɫɹ ɩɨɞ ɞɟɣɫɬɜɢɟɦ ɩɚɪɚɬɢɪɟɨɢɞɧɨɝɨ ɝɨɪɦɨɧɚ, ɹɜɥɹɸɳɟɝɨɫɹ ɜɚɠɧɵɦ ɤɨɦɩɨɧɟɧɬɨɦ ɧɢɲɢ ȽɋɄ. ɉɨɤɚɡɚɧɨ, ɱɬɨ ɩɪɨɬɟɨɦɧɵɣ ɚɧɚɥɢɡ ɦɨɠɟɬ ɩɪɢɦɟɧɹɬɶɫɹ ɞɥɹ ɧɚɛɥɸɞɟɧɢɹ ɡɚ ɞɢɧɚɦɢɤɨɣ ɢɡɦɟɧɟɧɢɹ ɛɟɥɤɨɜ ɜ ɨɬɜɟɬ ɧɚ ɜɧɟɲɧɢɟ ɜɨɡɞɟɣɫɬɜɢɹ, ɱɬɨ, ɜ ɫɜɨɸ ɨɱɟɪɟɞɶ,
ɞɚɫɬ ɜɨɡɦɨɠɧɨɫɬɶ ɩɪɨɜɨɞɢɬɶ ɷɤɫɩɚɧɫɢɸ ȽɋɄ ɜ ɭɫɥɨɜɢɹɯ in vitro.
3.
Ɉɩɢɫɚɧ ɩɪɨɬɟɨɦɧɵɣ ɩɪɨɮɢɥɶ ɆɇɄ ɢ CD34+ȽɋɄ ɫ ɜɵɫɨɤɢɦ
ɪɚɡɪɟɲɟɧɢɟɦ, ɬɨ ɟɫɬɶ ɫɞɟɥɚɧ ɜɚɠɧɵɣ ɲɚɝ ɜ ɩɨɫɬɪɨɟɧɢɢ ɝɥɨɛɚɥɶɧɨɝɨ
ɩɪɨɬɟɨɦɧɨɝɨ ɩɪɨɮɢɥɹ ɦɨɧɨɧɭɤɥɟɚɪɧɵɯ ɤɥɟɬɨɤ ɢ CD34+ ȽɋɄ. ɉɪɨɜɟɞɟɧɚ ɢɞɟɧɬɢɮɢɤɚɰɢɹ ɛɟɥɤɨɜ, ɩɪɢɫɭɬɫɬɜɭɸɳɢɯ ɜ CD34+ȽɋɄ.
4.
ɋɨɩɨɫɬɚɜɥɟɧɵ ɩɪɨɬɟɨɦɧɵɟ ɩɪɨɮɢɥɢ ɢɧɬɢɦɵ ɢ ɦɟɞɢɢ ɫɨɫɭ-
ɞɨɜ ɜ ɩɪɨɰɟɫɫɟ ɚɬɟɪɨɝɟɧɟɡɚ. ȼɵɹɜɥɟɧɵ ɛɟɥɤɢ, ɭɪɨɜɧɢ ɤɨɬɨɪɵɯ ɢɡɦɟɧɹɸɬɫɹ ɩɪɢ ɪɚɡɜɢɬɢɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɝɨ ɩɨɪɚɠɟɧɢɹ ɜ ɢɧɬɢɦɨɦɟɞɢɚɥɶɧɨɦ ɫɥɨɟ ɚɨɪɬɵ ɱɟɥɨɜɟɤɚ. ɉɨɞɬɜɟɪɠɞɟɧɚ ɪɨɥɶ ɜ ɮɨɪɦɢɪɨɜɚɧɢɢ ɚɬɟɪɨɫɤɥɟɪɨɬɢɱɟɫɤɨɣ ɛɥɹɲɤɢ ɬɚɤɢɯ ɧɢɡɤɨɦɨɥɟɤɭɥɹɪɧɵɯ ɛɟɥɤɨɜ,
ɤɚɤ ɚɧɧɟɤɫɢɧɵ ɢ ɛɟɥɤɢ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ.
111
5.
ɉɨɥɭɱɟɧɧɵɟ ɞɚɧɧɵɟ ɩɨɞɬɜɟɪɠɞɚɸɬ ɬɚɤɠɟ ɩɨɬɟɧɰɢɚɥɶɧɭɸ
ɜɨɡɦɨɠɧɨɫɬɶ ɢɫɩɨɥɶɡɨɜɚɧɢɹ ȽɋɄ ɜ ɬɟɪɚɩɢɢ ɚɬɟɪɨɫɤɥɟɪɨɡɚ ɢ ɭɤɚɡɵɜɚɸɬ
ɧɚ ɩɟɪɫɩɟɤɬɢɜɧɵɟ ɧɚɩɪɚɜɥɟɧɢɹ ɩɪɨɬɟɨɦɧɵɯ ɢɫɫɥɟɞɨɜɚɧɢɣ ɬɚɤɢɯ ɨɛɴɟɤɬɨɜ, ɤɚɤ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ, ɨɫɬɟɨɛɥɚɫɬɵ ɢ ɝɥɚɞɤɨɦɵɲɟɱɧɵɟ ɤɥɟɬɤɢ ɤɪɨɜɟɧɨɫɧɵɯ ɫɨɫɭɞɨɜ.
112
5. ɋɉɂɋɈɄ ɅɂɌȿɊȺɌɍɊɕ
1.
Ƚɚɣɤɨɜɚɹ Ʌ.Ȼ., Ʉɭɯɚɪɱɢɤ Ƚ.Ⱥ., ɇɟɫɬɟɪɨɜɚ ɇ.ɇ., ȼɚɜɢɥɨɜɚ
Ɍ.ȼ., Ȼɭɪɛɟɥɥɨ Ⱥ.Ɍ., ɒɚɛɪɨɜ Ⱥ.ȼ. ɋɨɜɪɟɦɟɧɧɵɟ ɥɚɛɨɪɚɬɨɪɧɵɟ ɦɚɪɤɟɪɵ ɜ ɨɩɪɟɞɟɥɟɧɢɢ ɩɪɨɝɧɨɡɚ ɩɪɢ ɨɫɬɪɨɦ ɤɨɪɨɧɚɪɧɨɦ ɫɢɧɞɪɨɦɟ ɢ ɦɨɧɢɬɨɪɢɧɝɟ ɬɟɪɚɩɢɢ // ȼɟɫɬɧɢɤ ɚɪɢɬɦɨɥɨɝɢɢ. – ʋ 58. – 2009. – ɋ. 52-59.
2.
ɉɟɬɪɨɜɚ Ɍ.ȼ., ɋɜɢɧɚɪɟɜɚ Ⱦ.Ⱥ., ɇɢɮɨɧɬɨɜɚ ɂ.ɇ. ɢ ɞɪ. ɋɬɪɨ-
ɦɚɥɶɧɚɹ ɪɟɝɭɥɹɰɢɹ ɫɬɜɨɥɨɜɵɯ ɤɪɨɜɟɬɜɨɪɧɵɯ ɤɥɟɬɨɤ ɜ ɞɥɢɬɟɥɶɧɵɯ
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ɝɨɪɦɨɧɚ // Ʉɥɟɬɨɱɧɵɟ ɬɟɯɧɨɥɨɝɢɢ ɜ ɛɢɨɥɨɝɢɢ ɢ ɦɟɞɢɰɢɧɟ. – 2006. - ʋ
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126
ɋɉɂɋɈɄ ɋɈɄɊȺɓȿɇɂɃ
ȽɋɄ – ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ
Ⱦɗ – ɞɜɭɦɟɪɧɵɟ ɷɥɟɤɬɪɨɮɨɪɟɝɪɚɦɦɵ
ɂɎȻ – ɢɡɨɬɨɧɢɱɟɫɤɢɣ ɮɨɫɮɚɬɧɵɣ ɛɭɮɟɪ, ɪɇ 7,4
ɂɗɎ – ɢɡɨɷɥɟɤɬɪɢɱɟɫɤɨɟ ɮɨɤɭɫɢɪɨɜɚɧɢɟ
Ʌɉɇɉ – ɥɢɩɨɩɪɨɬɟɢɞɵ ɧɢɡɤɨɣ ɩɥɨɬɧɨɫɬɢ
ɆɇɄ – ɦɨɧɨɧɭɤɥɟɚɪɧɵɟ ɤɥɟɬɤɢ
MCK – ɦɟɡɟɧɯɢɦɚɥɶɧɵɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ
ɉɄ – ɩɭɩɨɜɢɧɧɚɹ ɤɪɨɜɶ
ɉɌȽ – ɩɚɪɚɬɢɪɟɨɢɞɧɵɣ ɝɨɪɦɨɧ
ɋɄ – ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ
ɋɋɋ – ɫɟɪɞɟɱɧɨɫɨɫɭɞɢɫɬɚɹ ɫɢɫɬɟɦɚ
Ɍɏɍ – ɬɪɢɯɥɨɪɭɤɫɭɫɧɚɹ ɤɢɫɥɨɬɚ
ɎȻɋ – ɮɟɬɚɥɶɧɚɹ ɛɵɱɶɹ ɫɵɜɨɪɨɬɤɚ
ɗȾɌȺ – ɷɬɢɥɟɧɞɢɚɦɢɧɬɟɬɪɚɭɤɫɭɫɧɚɹ ɤɢɫɥɨɬɚ
CD34+ ȽɋɄ – ɝɟɦɨɩɨɷɬɢɱɟɫɤɢɟ ɫɬɜɨɥɨɜɵɟ ɤɥɟɬɤɢ, ɧɟɫɭɳɢɟ ɚɧɬɢɝɟɧ
CD34
2D – ɦɟɬɨɞ ɞɜɭɦɟɪɧɨɝɨ ɝɟɥɶ-ɷɥɟɤɬɪɨɮɨɪɟɡɚ ɧɚ ɩɨɥɢɚɤɪɢɥɚɦɢɞɟ
FACS – aɤɬɢɜɢɪɨɜɚɧɧɚɹ ɮɥɭɨɪɟɫɰɟɧɰɢɟɣ ɫɨɪɬɢɪɨɜɤɚ ɤɥɟɬɨɤ
GFP – ɡɟɥɟɧɵɣ ɮɥɭɨɪɟɫɰɢɪɭɸɳɢɣ ɛɟɥɨɤ
HSP – ɛɟɥɤɢ ɬɟɩɥɨɜɨɝɨ ɲɨɤɚ (heat-shock proteins )
IMDM – ɪɨɫɬɨɜɚɹ ɫɪɟɞɚ ɞɥɹ ɤɭɥɶɬɢɜɢɪɨɜɚɧɢɹ ɤɥɟɬɨɤ Dulbecco M
IPG ɫɬɪɢɩɵ – ɝɟɥɟɜɵɟ ɩɨɥɨɫɤɢ ɢɦɦɨɛɢɥɢɡɨɜɚɧɧɵɯ ɝɪɚɞɢɟɧɬɨɜ pH
IL – ɢɧɬɟɪɥɟɣɤɢɧ
Jagged1 (Jag1) – ɫɢɧɬɟɬɢɱɟɫɤɢɣ (ɦɵɲɢɧɵɣ) ɪɟɤɨɦɛɢɧɚɧɬɧɵɣ
ɩɟɩɬɢɞ, ɥɢɝɚɧɞ
127
MALDI–TOF (matrix assisted laser deionization time of flight) –
ɦɚɬɪɢɱɧɚɹ ɥɚɡɟɪɧɚɹ ɞɟɫɨɪɛɰɢɨɧɧɚɹ ɢɨɧɢɡɚɰɢɨɧɚɹ ɜɪɟɦɹɩɪɨɥɟɬɧɚɹ
ɦɚɫɫ-ɫɩɟɤɬɪɨɦɟɬɪɢɹ
Notch-1 – ɪɟɰɟɩɬɨɪ, ɩɪɢɫɭɬɫɬɜɭɸɳɢɣ ɧɚ ɩɨɜɟɪɯɧɨɫɬɢ ɤɥɟɬɨɤ
SCF – ɮɚɤɬɨɪ ɫɬɜɨɥɨɜɵɯ ɤɥɟɬɨɤ
TGF – ɬɪɚɧɫɮɨɪɦɢɪɭɸɳɢɣ ɮɚɤɬɨɪ ɪɨɫɬɚ
TPO – ɬɪɨɦɛɨɩɪɨɬɟɢɧ.
128
ɉɊɂɅɈɀȿɇɂȿ
Ȼɟɥɤɢ, ɢɞɟɧɬɢɮɢɰɢɪɨɜɚɧɧɵɟ ɦɟɬɨɞɚɦɢ
ɩɪɨɬɟɨɦɢɤɢ ɜ ɬɪɟɯ ɮɪɚɤɰɢɹɯ, ɜɵɞɟɥɟɧɧɵɯ ɢɡ CD34+ȽɋɄ
Ɍɚɛɥɢɰɚ 1
ȼɟɪɨɹɬɧɨɫɬɶ
ɇɨɦɟɪ
ʋ ɩ/ɩ ɫɨɜɩɚɞɟɧɢɹ
ɩɹɬɧɚ
ID ɛɟɥɤɨɜ ɞɥɹ CD34+ȽɋɄ (1-ɹ ɮɪɚɤɰɢɹ, 1-ɹ ɩɨɜɬɨɪɧɨɫɬɶ)
(%)
1
2
3
4
1
93.53
Immunoglobulin superfamily member 8 precursor CD81 partner 3
521
Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes
associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen
Homo sapiens Human
2
92.45
Hemoglobin subunit alpha Hemoglobin alpha chain Alpha globin
943
Homo sapiens Human
3
85.65
Hemoglobin subunit alpha Hemoglobin alpha chain Alpha globin
963
Homo sapiens Human
4
83.52
Immunoglobulin superfamily member 8 precursor CD81 partner 3
498
Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes
associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen
Homo sapiens Human
5
76.42
Hemoglobin subunit gamma 2 Hemoglobin gamma 2 chain Gamma
971
2 globin Hemoglobin gamma G chain Hb F Ggamma Homo sapiens
Human
6
68.30
Cystinosin Homo sapiens Human
773
7
68.18
Hemoglobin subunit gamma 1 Hemoglobin gamma 1 chain Gamma
786
1 globin Hemoglobin gamma A chain Hb F Agamma Homo sapiens
Human
8
58.09
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu583
man
9
56.07
Hemoglobin subunit gamma 2 Hemoglobin gamma 2 chain Gamma
806
2 globin Hemoglobin gamma G chain Hb F Ggamma Homo sapiens
Human
10
53.12
Vacuolar protein sorting associated protein 25 hVps25 ELL asso672
ciated protein of 20 kDa Dermal papilla derived protein 9 Homo
sapiens Human
11
48.43
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human
740
12
47.13
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu385
man
13
47.13
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu385
man
14
46.11
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu453
man
15
46.05
Immunoglobulin superfamily member 8 precursor CD81 partner 3
550
Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes
associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen
Homo sapiens Human
129
1
16
2
45.42
17
18
19
44.29
39.44
37.86
20
37.73
21
36.82
22
36.20
23
24
25
35.21
34.70
33.75
26
33.08
27
28.49
28
28.19
29
27.88
30
27.76
31
26.56
32
25.73
33
24.53
34
24.18
35
23.66
36
23.54
3
Immunoglobulin superfamily member 8 precursor CD81 partner 3
Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes
associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen
Homo sapiens Human
Chloride channel protein 3 ClC 3 Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Immunoglobulin superfamily member 8 precursor CD81 partner 3
Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes
associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen
Homo sapiens Human
Epididymal-specific lipocalin 9 precursor MUP like lipocalin Homo
sapiens Human
Low-density lipoprotein receptor related protein 8 precursor Apolipoprotein E receptor 2 Homo sapiens Human
Hemoglobin subunit gamma 1 Hemoglobin gamma 1 chain Gamma
1 globin Hemoglobin gamma A chain Hb F Agamma Homo sapiens
Human
Uncharacterized protein KIAA0196 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Epididymal-specific lipocalin 9 precursor MUP like lipocalin Homo
sapiens Human
Vacuolar protein sorting associated protein 25 hVps25 ELL associated protein of 20 kDa Dermal papilla derived protein 9 Homo
sapiens Human
Selenocysteine-specific elongation factor Elongation factor sec Eukaryotic elongation factor selenocysteine tRNA specific Homo sapiens Human
Immunoglobulin superfamily member 8 precursor CD81 partner 3
Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes
associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen
Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human
Immunoglobulin superfamily member 8 precursor CD81 partner 3
Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes
associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen
Homo sapiens Human
DNA-directed RNA polymerase mitochondrial precursor EC 2 7 7 6
MtRPOL Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human
Hemoglobin subunit gamma 2 Hemoglobin gamma 2 chain Gamma
2 globin Hemoglobin gamma G chain Hb F Ggamma Homo sapiens
Human
Transcription factor MafK Erythroid transcription factor NF E2 p18
subunit Homo sapiens Human
4
528
597
1017
630
970
901
814
588
883
788
491
593
629
598
640
591
581
736
522
851
611
130
1
37
2
22.94
38
22.57
39
22.53
40
22.37
41
42
43
44
22.34
22.34
22.34
21.74
45
21.28
46
20.71
47
48
49
50
20.70
20.48
20.45
20.10
51
19.29
52
19.04
53
19.03
54
18.76
55
18.75
56
18.75
57
58
59
17.59
17.59
17.37
60
61
62
63
64
17.27
17.27
16.13
15.91
15.87
3
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human
Immunoglobulin superfamily member 8 precursor CD81 partner 3
Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes
associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen
Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Beta-defensin 118 precursor Defensin beta 118 Beta defensin 18
DEFB 18 Epididymal secretory protein 13 6 ESP13 6 Homo sapiens
Human
Actin-binding Rho activating protein Striated muscle activator of
Rho dependent signaling STARS Homo sapiens Human
Beta-defensin 118 precursor Defensin beta 118 Beta defensin 18
DEFB 18 Epididymal secretory protein 13 6 ESP13 6 Homo sapiens
Human
Uncharacterized protein C9orf79 Homo sapiens Human
Uncharacterized protein C9orf79 Homo sapiens Human
Glial fibrillary acidic protein astrocyte GFAP Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97
kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human
Epididymal-specific lipocalin 9 precursor MUP like lipocalin Homo
sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
kDa nucleoporin Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Olfactory receptor 51G1 Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Mitochondrial intermediate peptidase mitochondrial precursor EC 3
4 24 59 MIP Homo sapiens Human
4
599
555
713
480
283
283
283
849
621
807
728
715
684
446
896
548
1023
1035
392
392
263
263
571
254
254
699
648
761
131
1
65
2
15.73
66
67
15.58
15.48
68
69
15.14
14.77
70
14.77
71
72
14.71
14.01
73
13.95
74
13.67
75
76
77
78
13.60
13.60
12.98
12.87
79
12.87
80
81
12.51
12.12
82
12.06
83
84
11.90
11.85
85
86
87
11.59
11.59
11.56
88
11.56
3
Actin-binding Rho activating protein Striated muscle activator of
Rho dependent signaling STARS Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator of
Rho dependent signaling STARS Homo sapiens Human
Immunoglobulin superfamily member 8 precursor CD81 partner 3
Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes
associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen
Homo sapiens Human
Prolargin precursor Proline arginine rich end leucine rich repeat
protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Uncharacterized protein C9orf79 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
HpaII tiny fragments locus 9c protein Homo sapiens Human
Immunoglobulin superfamily member 8 precursor CD81 partner 3
Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes
associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen
Homo sapiens Human
Immunoglobulin superfamily member 8 precursor CD81 partner 3
Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes
associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen
Homo sapiens Human
Uncharacterized protein KIAA0196 Homo sapiens Human
FYN-binding protein FYN T binding protein FYB 120 130 p120
p130 SLP 76 associated phosphoprotein SLAP 130 Adhesion and
degranulation promoting adaptor protein ADAP Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
4
600
650
763
559
355
355
665
513
512
717
257
257
558
377
377
782
582
743
508
606
302
302
247
247
132
1
89
90
2
11.40
11.22
91
92
93
94
95
11.19
11.19
11.02
11.00
10.99
96
10.99
97
10.87
98
10.87
99
10.77
100
10.74
101
102
103
104
10.67
10.64
10.55
10.54
105
10.26
106
10.06
107
9.90
108
109
9.90
9.79
110
111
9.64
9.59
112
113
114
115
116
117
118
119
120
9.57
9.57
9.45
9.43
9.37
9.37
9.36
9.36
9.28
121
122
9.21
9.10
3
Uncharacterized protein C9orf79 Homo sapiens Human
E3 ubiquitin protein ligase RNF19 EC 6 3 2 RING finger protein 19
Dorfin Double ring finger protein p38 protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Zinc finger BED domain containing protein 4 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing
protein 21 Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human
E3
Angiopoietin-1 precursor ANG 1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
kDa nucleoporin Homo sapiens Human
Anaphase-promoting complex subunit 2 APC2 Cyclosome subunit 2
Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
kDa nucleoporin Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
kDa nucleoporin Homo sapiens Human
Glial fibrillary acidic protein astrocyte GFAP Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Cathepsin S precursor EC 3 4 22 27 Homo sapiens Human
Cathepsin S precursor EC 3 4 22 27 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2
Telomeric DNA binding protein Homo sapiens Human
Uncharacterized protein C9orf79 Homo sapiens Human
Beta-defensin 118 precursor Defensin beta 118 Beta defensin 18
DEFB 18 Epididymal secretory protein 13 6 ESP13 6 Homo sapiens
Human
4
494
601
252
252
646
484
359
359
376
376
752
608
997
467
958
553
836
514
542
542
636
562
466
285
285
711
934
239
239
289
289
637
724
841
133
1
123
124
125
126
2
9.01
9.01
8.82
8.69
127
8.69
128
8.68
129
8.60
130
8.60
131
8.55
132
8.55
133
134
135
136
8.46
8.18
8.18
8.10
137
138
139
140
141
142
143
8.00
8.00
7.99
7.95
7.90
7.90
7.88
144
7.88
145
7.86
146
7.86
147
7.84
148
7.84
149
7.84
150
7.77
3
4
Keratin-associated protein 21 2 Homo sapiens Human
246
Keratin-associated protein 21 2 Homo sapiens Human
246
Uncharacterized protein C18orf54 precursor Homo sapiens Human
472
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
400
kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
400
kDa nucleoporin Homo sapiens Human
Vacuolar protein sorting associated protein 25 hVps25 ELL asso1033
ciated protein of 20 kDa Dermal papilla derived protein 9 Homo
sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur232
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur232
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20 Ho371
mo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20 Ho371
mo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
428
Keratin-associated protein 21 2 Homo sapiens Human
277
Keratin-associated protein 21 2 Homo sapiens Human
277
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
1024
Human
Keratin-associated protein 21 2 Homo sapiens Human
275
Keratin-associated protein 21 2 Homo sapiens Human
275
Zinc finger protein 225 Homo sapiens Human
420
Keratin-associated protein 21 2 Homo sapiens Human
975
Angiopoietin-1 precursor ANG 1 Homo sapiens Human
344
Angiopoietin-1 precursor ANG 1 Homo sapiens Human
344
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
381
protein Atrophin 1 related protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
381
protein Atrophin 1 related protein Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur320
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur320
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
408
kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
408
kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
408
kDa nucleoporin Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
518
protein Atrophin 1 related protein Homo sapiens Human
134
1
151
2
7.74
152
153
7.69
7.66
154
155
156
7.58
7.58
7.57
157
158
159
160
7.47
7.47
7.47
7.29
161
7.29
162
163
7.23
7.13
164
7.10
165
7.09
166
167
7.08
7.05
168
7.05
169
7.02
170
6.98
171
6.98
172
6.95
173
6.95
174
6.88
175
6.72
3
Vacuolar ATP synthase subunit G 2 EC 3 6 3 14 V ATPase G subunit 2 Vacuolar proton pump G subunit 2 V ATPase 13 kDa subunit
2 Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Vacuolar protein sorting associated protein 25 hVps25 ELL associated protein of 20 kDa Dermal papilla derived protein 9 Homo
sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
MANSC domain containing protein 1 precursor Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2
Telomeric DNA binding protein Homo sapiens Human
Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2
Telomeric DNA binding protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Zinc finger and BTB domain containing protein 41 Homo sapiens
Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
Human
Bcl-2-modifying factor Homo sapiens Human
Putative tyrosine protein phosphatase TPTE EC 3 1 3 48 Transmembrane phosphatase with tensin homology Protein BJ HCC 5 Homo
sapiens Human
Putative tyrosine protein phosphatase TPTE EC 3 1 3 48 Transmembrane phosphatase with tensin homology Protein BJ HCC 5 Homo
sapiens Human
Transcription factor MafK Erythroid transcription factor NF E2 p18
subunit Homo sapiens Human
Brevican core protein precursor Brain enriched hyaluronan binding
protein Protein BEHAB Homo sapiens Human
Brevican core protein precursor Brain enriched hyaluronan binding
protein Protein BEHAB Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
4
776
457
410
290
290
892
305
305
305
405
405
944
923
516
917
953
388
388
766
409
409
351
351
488
368
135
1
176
2
6.72
177
178
179
180
6.71
6.71
6.71
6.66
181
6.64
182
183
184
6.57
6.57
6.50
185
6.50
186
6.46
187
6.43
188
6.43
189
190
6.33
6.31
191
6.31
192
6.31
193
6.25
194
6.25
195
6.20
196
6.20
197
6.17
198
6.09
199
200
201
6.08
5.95
5.93
202
5.93
3
4
Complex I intermediate associated protein 30 mitochondrial precur368
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Zinc finger BED domain containing protein 4 Homo sapiens Human 380
Zinc finger BED domain containing protein 4 Homo sapiens Human 380
Zinc finger BED domain containing protein 4 Homo sapiens Human 380
Epididymal-specific lipocalin 9 precursor MUP like lipocalin Homo
797
sapiens Human
Beta-defensin 118 precursor Defensin beta 118 Beta defensin 18
771
DEFB 18 Epididymal secretory protein 13 6 ESP13 6 Homo sapiens
Human
Angiopoietin-1 precursor ANG 1 Homo sapiens Human
328
Angiopoietin-1 precursor ANG 1 Homo sapiens Human
328
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu725
man
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu725
man
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
425
protein Atrophin 1 related protein Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur379
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur379
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Uncharacterized protein C18orf54 precursor Homo sapiens Human
492
Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2
406
Telomeric DNA binding protein Homo sapiens Human
Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2
406
Telomeric DNA binding protein Homo sapiens Human
Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2
406
Telomeric DNA binding protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
397
protein Atrophin 1 related protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
397
protein Atrophin 1 related protein Homo sapiens Human
Zinc finger protein ZFPM2 Zinc finger protein multitype 2 Friend of 231
GATA protein 2 FOG 2 hFOG 2 Homo sapiens Human
Zinc finger protein ZFPM2 Zinc finger protein multitype 2 Friend of 231
GATA protein 2 FOG 2 hFOG 2 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
634
kDa nucleoporin Homo sapiens Human
PHD finger protein 21A BRAF35 HDAC complex protein BHC80
1039
BHC80a Homo sapiens Human
Biotinidase precursor EC 3 5 1 12 Homo sapiens Human
915
Secretagogin Homo sapiens Human
946
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu573
man
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu573
man
136
1
203
2
5.86
204
205
206
207
5.84
5.79
5.79
5.78
208
5.78
209
5.76
210
5.72
211
5.72
212
5.70
213
5.70
214
5.67
215
216
5.66
5.59
217
218
5.58
5.51
219
5.51
220
5.50
221
5.42
222
5.39
223
5.38
224
225
226
227
228
229
5.36
5.36
5.35
5.35
5.34
5.32
3
4
Complex I intermediate associated protein 30 mitochondrial precur677
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
688
Keratin-associated protein 21 2 Homo sapiens Human
644
Keratin-associated protein 21 2 Homo sapiens Human
644
Complex I intermediate associated protein 30 mitochondrial precur297
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur297
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Hepatocyte nuclear factor 3 alpha HNF 3A Forkhead box protein A1 867
Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
363
kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
363
kDa nucleoporin Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur308
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur308
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu703
man
Keratin-associated protein 21 2 Homo sapiens Human
855
Cytochrome P450 2W1 EC 1 14 14 CYPIIW1 Homo sapiens Hu770
man
Immunoglobulin J chain Homo sapiens Human
887
Sulfhydryl oxidase 1 precursor EC 1 8 3 2 Quiescin Q6 hQSOX
504
Homo sapiens Human
Sulfhydryl oxidase 1 precursor EC 1 8 3 2 Quiescin Q6 hQSOX
504
Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
757
kDa nucleoporin Homo sapiens Human
Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2
614
Telomeric DNA binding protein Homo sapiens Human
Serine/threonine-protein kinase 17B EC 2 7 11 1 DAP kinase related 858
apoptosis inducing protein kinase 2 Homo sapiens Human
Group IIF secretory phospholipase A2 precursor EC 3 1 1 4 Phos881
phatidylcholine 2 acylhydrolase GIIF GIIF sPLA2 sPLA 2 IIF Homo
sapiens Human
Bcl-2-modifying factor Homo sapiens Human
546
Bcl-2-modifying factor Homo sapiens Human
546
Keratin-associated protein 21 2 Homo sapiens Human
286
Keratin-associated protein 21 2 Homo sapiens Human
286
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human
1042
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
435
Human
137
1
230
2
5.32
231
5.31
232
5.31
233
5.30
234
5.30
235
5.30
236
5.29
237
5.24
238
5.12
239
5.12
240
5.11
241
5.10
242
5.07
243
5.07
244
5.04
245
246
247
5.02
5.02
4.99
248
4.97
249
4.96
250
4.96
251
252
253
4.95
4.95
4.86
3
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
Human
Actin-binding Rho activating protein Striated muscle activator of
Rho dependent signaling STARS Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator of
Rho dependent signaling STARS Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
kDa nucleoporin Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
kDa nucleoporin Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator of
Rho dependent signaling STARS Homo sapiens Human
PHD finger protein 21A BRAF35 HDAC complex protein BHC80
BHC80a Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Syntaxin-binding protein 1 Unc 18 homolog Unc 18A Unc 18 1 N
Sec1 p67 Homo sapiens Human
Bifunctional
Bifunctional
Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6
tetrakisphosphate 5 kinase Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6
tetrakisphosphate 5 kinase Homo sapiens Human
Zinc finger protein 225 Homo sapiens Human
Zinc finger protein 225 Homo sapiens Human
Mitogen-activated protein kinase kinase kinase 15 EC 2 7 11 25
MAPK ERK kinase kinase 15 MEK kinase 15 MEKK 15 Homo
sapiens Human
4
435
499
499
401
401
401
523
768
343
343
638
723
864
864
412
260
260
720
575
398
398
541
541
809
138
1
254
2
4.77
255
4.76
256
257
4.71
4.70
258
259
260
261
262
263
264
265
4.68
4.62
4.62
4.62
4.62
4.62
4.62
4.61
266
4.60
267
4.60
268
4.59
269
4.57
270
271
272
273
4.56
4.56
4.56
4.50
274
4.50
275
4.47
276
4.43
277
4.43
278
4.43
279
4.42
280
4.39
281
282
283
4.37
4.37
4.29
3
4
Cadherin-like protein 26 precursor Cadherin like protein VR20 Ho707
mo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
900
Human
Bcl-2-modifying factor Homo sapiens Human
655
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
1025
Human
Bcl-2-modifying factor Homo sapiens Human
628
Keratin-associated protein 21 2 Homo sapiens Human
251
Keratin-associated protein 21 2 Homo sapiens Human
251
Keratin-associated protein 21 2 Homo sapiens Human
251
Keratin-associated protein 21 2 Homo sapiens Human
251
Keratin-associated protein 21 2 Homo sapiens Human
251
Keratin-associated protein 21 2 Homo sapiens Human
251
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu565
man
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
386
protein Atrophin 1 related protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
386
protein Atrophin 1 related protein Homo sapiens Human
Zinc finger protein 96 Zinc finger protein 305 Zinc finger and SCAN 779
domain containing protein 12 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
423
protein Atrophin 1 related protein Homo sapiens Human
Zinc finger protein 677 Homo sapiens Human
517
Zinc finger protein 677 Homo sapiens Human
517
Zinc finger protein 677 Homo sapiens Human
517
Regenerating islet derived protein 4 precursor Reg IV REG like
327
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
327
protein Gastrointestinal secretory protein Homo sapiens Human
Serine/threonine-protein kinase VRK1 EC 2 7 11 1 Vaccinia related
778
kinase 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur248
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur248
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur248
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
586
protein Atrophin 1 related protein Homo sapiens Human
Keratin, type I cytoskeletal 9 Cytokeratin 9 CK 9 Keratin 9 K9 Ho1032
mo sapiens Human
Ig lambda chain V II region TRO Homo sapiens Human
603
Ig lambda chain V II region TRO Homo sapiens Human
603
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu552
man
139
1
284
285
286
287
2
4.28
4.27
4.27
4.26
288
4.26
289
4.23
290
4.22
291
4.22
292
4.19
293
4.19
294
4.18
295
296
297
4.17
4.13
4.12
298
4.12
299
300
4.11
4.09
301
302
303
304
305
4.08
4.08
4.08
4.08
4.03
306
4.02
307
308
309
3.98
3.98
3.97
3
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Uncharacterized protein C21orf62 B37 Homo sapiens Human
Vacuolar protein sorting associated protein 25 hVps25 ELL associated protein of 20 kDa Dermal papilla derived protein 9 Homo
sapiens Human
Profilin-3 Profilin III Homo sapiens Human
Profilin-3 Profilin III Homo sapiens Human
Profilin-3 Profilin III Homo sapiens Human
Profilin-3 Profilin III Homo sapiens Human
Vacuolar ATP synthase subunit G 2 EC 3 6 3 14 V ATPase G subunit 2 Vacuolar proton pump G subunit 2 V ATPase 13 kDa subunit
2 Homo sapiens Human
Trans-Golgi network integral membrane protein 2 precursor Trans
Golgi network protein TGN51 TGN46 TGN48 TGN38 homolog
Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
4
427
300
300
259
259
647
676
676
374
374
589
679
765
326
326
416
476
244
244
244
244
824
829
976
976
390
140
1
310
2
3.97
311
3.97
312
3.96
313
3.96
314
3.94
315
3.94
316
3.92
317
3.92
318
3.92
319
3.90
320
3.90
321
3.87
322
3.87
323
324
3.85
3.80
325
3.75
326
3.73
327
3.71
328
3.71
329
3.71
330
3.67
331
3.65
3
4
Complex I intermediate associated protein 30 mitochondrial precur390
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur390
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
954
Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
954
Human
Presequence protease mitochondrial precursor EC 3 4 24 hPreP
407
Pitrilysin metalloproteinase 1 Metalloprotease 1 hMP1 Homo sapiens Human
Presequence protease mitochondrial precursor EC 3 4 24 hPreP
407
Pitrilysin metalloproteinase 1 Metalloprotease 1 hMP1 Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20 Ho572
mo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20 Ho572
mo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20 Ho572
mo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu631
man
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu631
man
Complex I intermediate associated protein 30 mitochondrial precur340
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur340
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Glial fibrillary acidic protein astrocyte GFAP Homo sapiens Human
460
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
566
protein Atrophin 1 related protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
712
protein Atrophin 1 related protein Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur463
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu337
man
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu337
man
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu337
man
Keratin, type I cytoskeletal 9 Cytokeratin 9 CK 9 Keratin 9 K9 Ho1016
mo sapiens Human
Microtubule-associated protein 9 Aster associated protein Homo
240
sapiens Human
141
1
332
2
3.65
333
334
3.62
3.61
335
3.61
336
3.60
337
3.60
338
3.60
339
3.59
340
3.59
341
3.59
342
3.58
343
344
345
346
347
3.55
3.54
3.54
3.53
3.51
348
3.50
349
3.50
350
3.49
351
3.49
352
3.49
353
3.47
354
3.47
355
356
3.46
3.44
357
3.44
3
Microtubule-associated protein 9 Aster associated protein Homo
sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Ubiquitin carboxyl terminal hydrolase 42 EC 3 1 2 15 Ubiquitin
thioesterase 42 Ubiquitin specific processing protease 42 Deubiquitinating enzyme 42 Homo sapiens Human
Ubiquitin carboxyl terminal hydrolase 42 EC 3 1 2 15 Ubiquitin
thioesterase 42 Ubiquitin specific processing protease 42 Deubiquitinating enzyme 42 Homo sapiens Human
PR domain zinc finger protein 6 PR domain containing protein 6
Fragment Homo sapiens Human
PR domain zinc finger protein 6 PR domain containing protein 6
Fragment Homo sapiens Human
PR domain zinc finger protein 6 PR domain containing protein 6
Fragment Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human
Zinc finger protein 225 Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Chloride channel protein 6 ClC 6 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
4
240
651
438
438
578
578
578
324
324
324
464
418
375
375
842
888
318
318
316
316
316
323
323
747
315
315
142
1
358
2
3.44
359
3.43
360
3.43
361
3.42
362
3.42
363
3.42
364
3.42
365
3.40
366
3.40
367
3.39
368
3.38
369
370
371
3.37
3.37
3.35
372
373
3.33
3.32
374
3.32
375
376
3.31
3.30
377
3.30
378
3.30
379
3.29
380
3.29
381
3.27
382
3.26
383
3.26
3
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator of
Rho dependent signaling STARS Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator of
Rho dependent signaling STARS Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6
tetrakisphosphate 5 kinase Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6
tetrakisphosphate 5 kinase Homo sapiens Human
Ligand-dependent corepressor LCoR Mblk1 related protein 2 Homo
sapiensHuman
B-lymphocyte antigen CD19 precursor Differentiation antigen CD19
B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Kinesin-like protein KIF3A Microtubule plus end directed kinesin
motor 3A Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
4
315
758
758
296
296
296
296
602
602
952
962
701
701
882
880
570
570
933
279
279
279
661
661
908
335
335
143
1
384
385
386
387
388
2
3.25
3.25
3.25
3.25
3.23
389
3.23
390
3.22
391
3.20
392
3.20
393
3.20
394
3.20
395
3.20
396
397
3.19
3.18
398
3.18
399
3.18
400
3.18
401
3.17
402
3.17
403
3.17
404
3.16
405
3.16
3
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing
protein 21 Homo sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing
protein 21 Homo sapiens Human
Rho guanine nucleotide exchange factor 5 Guanine nucleotide regulatory protein TIM Oncogene TIM p60 TIM Transforming immortalized mammary oncogene Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
MARVEL domain containing protein 1 Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97
kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97
kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97
kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97
kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
4
226
226
226
226
426
426
592
309
309
309
309
309
948
396
396
396
396
356
356
356
429
429
144
1
406
2
3.13
407
3.12
408
3.08
409
410
411
412
3.07
3.07
3.07
3.03
413
414
3.01
3.00
415
3.00
416
2.98
417
2.98
418
2.97
419
2.93
420
2.92
421
2.92
422
2.89
423
2.89
424
2.89
425
2.89
426
2.89
427
428
2.88
2.87
3
4
Teratocarcinoma-derived growth factor 1 precursor Epidermal
982
growth factor like cripto protein CR1 Cripto 1 growth factor CRGF
Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
755
kDa nucleoporin Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97
531
kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
270
Keratin-associated protein 21 2 Homo sapiens Human
270
Keratin-associated protein 21 2 Homo sapiens Human
270
Cadherin-like protein 26 precursor Cadherin like protein VR20 Ho440
mo sapiens Human
Protein yippee like 4 Homo sapiens Human
434
Complex I intermediate associated protein 30 mitochondrial precur346
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur346
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Zona pellucida sperm binding protein 2 precursor Zona pellucida
301
glycoprotein ZP2 Zona pellucida protein A Homo sapiens Human
Zona pellucida sperm binding protein 2 precursor Zona pellucida
301
glycoprotein ZP2 Zona pellucida protein A Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
671
protein Gastrointestinal secretory protein Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20 Ho421
mo sapiens Human
Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2
635
Telomeric DNA binding protein Homo sapiens Human
Telomeric repeat binding factor 2 TTAGGG repeat binding factor 2
635
Telomeric DNA binding protein Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur310
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur310
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur310
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur310
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur310
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Protein mago nashi homolog Homo sapiens Human
1046
Lipoma HMGIC fusion partner like 2 protein Homo sapiens Human
470
145
1
429
430
2
2.87
2.86
431
2.86
432
2.86
433
2.85
434
2.84
435
2.84
436
2.81
437
2.81
438
2.80
439
440
441
442
443
2.79
2.79
2.79
2.77
2.75
444
2.75
445
2.73
446
2.72
447
2.71
448
2.70
449
2.69
450
2.69
451
2.67
452
2.67
453
2.66
3
4
Lipoma HMGIC fusion partner like 2 protein Homo sapiens Human
470
Regenerating islet derived protein 4 precursor Reg IV REG like
278
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
278
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
278
protein Gastrointestinal secretory protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
574
protein Atrophin 1 related protein Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
505
kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
505
kDa nucleoporin Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
652
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
652
protein Gastrointestinal secretory protein Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Hu482
man
Transmembrane protein 106B Homo sapiens Human
436
Transmembrane protein 106B Homo sapiens Human
436
Transmembrane protein 106B Homo sapiens Human
436
Protein mago nashi homolog Homo sapiens Human
991
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6
404
tetrakisphosphate 5 kinase Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6
404
tetrakisphosphate 5 kinase Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur525
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
PHD finger protein 21A BRAF35 HDAC complex protein BHC80
619
BHC80a Homo sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing
678
protein 21 Homo sapiens Human
F-box/WD repeat protein 5 F box and WD 40 domain protein 5
642
Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
272
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
272
protein Gastrointestinal secretory protein Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur530
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur530
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Rho guanine nucleotide exchange factor 5 Guanine nucleotide regu- 1022
latory protein TIM Oncogene TIM p60 TIM Transforming immortalized mammary oncogene Homo sapiens Human
146
1
454
455
2
2.65
2.64
456
457
458
2.63
2.63
2.62
459
2.61
460
2.61
461
2.60
462
463
464
465
466
2.59
2.59
2.59
2.59
2.57
467
468
2.56
2.53
469
2.50
470
471
2.49
2.48
472
2.48
473
2.47
474
2.45
475
2.45
476
2.45
477
478
479
480
481
2.40
2.40
2.39
2.36
2.36
3
Protein mago nashi homolog Homo sapiens Human
Nucleolar complex protein 4 homolog NOC4 protein homolog
NOC4 like protein Nucleolar complex associated protein 4 like
protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Epididymal-specific lipocalin 9 precursor MUP like lipocalin Homo
sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human
Acetylcholine receptor subunit epsilon precursor Homo sapiens
Human
Bcl-2-modifying factor Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Rho guanine nucleotide exchange factor 5 Guanine nucleotide regulatory protein TIM Oncogene TIM p60 TIM Transforming immortalized mammary oncogene Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Sclerostin domain containing protein 1 precursor Ectodermal BMP
inhibitor Ectodin Uterine sensitization associated gene 1 protein
USAG 1 Homo sapiens Human
Hemoglobin subunit gamma 2 Hemoglobin gamma 2 chain Gamma
2 globin Hemoglobin gamma G chain Hb F Ggamma Homo sapiens
Human
Beta-arrestin-2 Arrestin beta 2 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
Human
Multiple epidermal growth factor like domains 6 precursor EGF like
domain containing protein 3 Multiple EGF like domain protein 3
Homo sapiens Human
Multiple epidermal growth factor like domains 6 precursor EGF like
domain containing protein 3 Multiple EGF like domain protein 3
Homo sapiens Human
Multiple epidermal growth factor like domains 6 precursor EGF like
domain containing protein 3 Multiple EGF like domain protein 3
Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Zinc finger BED domain containing protein 4 Homo sapiens Human
Angiopoietin-1 precursor ANG 1 Homo sapiens Human
Angiopoietin-1 precursor ANG 1 Homo sapiens Human
4
907
893
311
311
828
330
330
750
329
329
329
329
479
990
902
940
687
545
545
1003
373
373
373
670
670
411
459
459
147
1
482
483
484
2
2.35
2.35
2.34
485
2.34
486
2.30
487
2.30
488
2.29
489
2.27
490
2.27
491
2.26
492
2.26
493
2.26
494
2.24
495
2.21
496
2.21
497
2.19
498
499
500
2.16
2.15
2.14
501
2.14
502
2.12
503
2.12
504
2.10
505
2.10
3
Zinc finger BED domain containing protein 4 Homo sapiens Human
Zinc finger BED domain containing protein 4 Homo sapiens Human
Acyl-CoA-binding domain containing protein 7 Homo sapiens Human
Acyl-CoA-binding domain containing protein 7 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Beta-defensin 118 precursor Defensin beta 118 Beta defensin 18
DEFB 18 Epididymal secretory protein 13 6 ESP13 6 Homo sapiens
Human
POU domain class 5 transcription factor 1 like protein 1 Octamer
binding protein 3 like Homo sapiens Human
POU domain class 5 transcription factor 1 like protein 1 Octamer
binding protein 3 like Homo sapiens Human
Late cornified envelope protein 3C Late envelope protein 15 Small
proline rich like epidermal differentiation complex protein 3A Homo
sapiens Human
Late cornified envelope protein 3C Late envelope protein 15 Small
proline rich like epidermal differentiation complex protein 3A Homo
sapiens Human
Late cornified envelope protein 3C Late envelope protein 15 Small
proline rich like epidermal differentiation complex protein 3A Homo
sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Zinc finger protein 691 Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Major prion protein precursor PrP PrP27 30 PrP33 35C ASCR
CD230 antigen Homo sapiens Human
Major prion protein precursor PrP PrP27 30 PrP33 35C ASCR
CD230 antigen Homo sapiens Human
4
764
764
364
364
455
455
826
874
874
298
298
298
474
520
520
444
624
413
689
689
312
312
515
515
148
1
506
2
2.10
507
508
2.09
2.08
509
2.07
510
2.05
511
2.05
512
2.05
513
514
515
2.04
2.04
2.03
516
2.01
517
2.01
518
2.01
519
2.01
520
2.01
521
2.00
522
1.99
523
1.99
524
1.99
525
1.96
526
527
528
529
530
531
1.95
1.95
1.92
1.91
1.91
1.90
532
1.88
3
Major prion protein precursor PrP PrP27 30 PrP33 35C ASCR
CD230 antigen Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
PHD finger protein 21A BRAF35 HDAC complex protein BHC80
BHC80a Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator of
Rho dependent signaling STARS Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Ly6/PLAUR domain containing protein 3 precursor GPI anchored
metastasis associated protein C4 4A homolog Matrigel induced gene
C4 protein MIG C4 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
Human
Uncharacterized protein C10orf38 precursor Astroprincin Homo
sapiens Human
Protein transport protein Sec24D SEC24 related protein D Homo
sapiens Human
Protein transport protein Sec24D SEC24 related protein D Homo
sapiens Human
Protein transport protein Sec24D SEC24 related protein D Homo
sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
Cathepsin S precursor EC 3 4 22 27 Homo sapiens Human
Zinc finger protein 225 Homo sapiens Human
Zinc finger protein 225 Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
4
515
955
729
506
341
341
341
978
978
903
242
242
242
242
242
667
443
443
443
456
448
448
445
430
430
584
422
149
1
533
2
1.88
534
535
1.87
1.85
536
1.83
537
1.83
538
1.81
539
1.81
540
1.80
541
1.80
542
1.79
543
1.78
544
1.77
545
1.71
546
1.71
547
1.70
548
1.70
549
1.69
550
1.67
551
1.63
552
1.61
553
1.60
554
1.60
555
1.58
556
1.58
3
4
Complex I intermediate associated protein 30 mitochondrial precur422
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Protein ARMCX6 Homo sapiens Human
560
Glia-activating factor precursor GAF Fibroblast growth factor 9 FGF 941
9 HBGF 9 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
680
Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
680
Human
Complex I intermediate associated protein 30 mitochondrial precur249
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precur249
sor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
461
protein Atrophin 1 related protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
461
protein Atrophin 1 related protein Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
996
Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
719
protein Atrophin 1 related protein Homo sapiens Human
Glycine cleavage system H protein mitochondrial precursor Homo
850
sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
663
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
663
protein Gastrointestinal secretory protein Homo sapiens Human
Replication protein A 14 kDa subunit RP A RF A Replication factor 255
A protein 3 p14 Homo sapiens Human
Replication protein A 14 kDa subunit RP A RF A Replication factor 255
A protein 3 p14 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
716
protein Atrophin 1 related protein Homo sapiens Human
Epididymal-specific lipocalin 9 precursor MUP like lipocalin Homo
804
sapiens Human
Homeobox protein OTX2 Orthodenticle homolog 2 Homo sapiens
798
Human
Regenerating islet derived protein 4 precursor Reg IV REG like
1009
protein Gastrointestinal secretory protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
577
protein Atrophin 1 related protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
577
protein Atrophin 1 related protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
262
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
262
protein Gastrointestinal secretory protein Homo sapiens Human
150
1
557
558
559
560
561
562
563
2
1.56
1.56
1.56
1.55
1.55
1.55
1.53
564
1.52
565
1.52
566
1.51
567
1.51
568
1.50
569
1.50
570
571
572
1.48
1.48
1.47
573
1.47
574
1.46
575
1.46
576
1.45
577
1.45
578
579
580
581
582
1.44
1.44
1.43
1.43
1.41
583
1.40
584
1.39
3
Arylsulfatase J precursor EC 3 1 6 ASJ Homo sapiens Human
Arylsulfatase J precursor EC 3 1 6 ASJ Homo sapiens Human
Arylsulfatase J precursor EC 3 1 6 ASJ Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
L-lactate dehydrogenase B chain EC 1 1 1 27 LDH B LDH heart
subunit LDH H Renal carcinoma antigen NY REN 46 Homo sapiens
Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
HLA class II histocompatibility antigen DM beta chain precursor
MHC class II antigen DMB Homo sapiens Human
HLA class II histocompatibility antigen DM beta chain precursor
MHC class II antigen DMB Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
kDa nucleoporin Homo sapiens Human
Putative uncharacterized protein C10orf130 Homo sapiens Human
Putative uncharacterized protein C10orf130 Homo sapiens Human
Kv channel interacting protein 1 KChIP1 A type potassium channel
modulatory protein 1 Potassium channel interacting protein 1 Vesicle
APC binding protein Homo sapiens Human
Kv channel interacting protein 1 KChIP1 A type potassium channel
modulatory protein 1 Potassium channel interacting protein 1 Vesicle
APC binding protein Homo sapiens Human
Olfactory receptor 2H1 Olfactory receptor OR6 32 Hs6M1 16 Olfactory
receptor 6 2 OR6 2 OLFR42A 9004 14 9026 2 Homo sapiens Human
Olfactory receptor 2H1 Olfactory receptor OR6 32 Hs6M1 16 Olfactory receptor 6 2 OR6 2 OLFR42A 9004 14 9026 2 Homo sapiens
Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
Phosducin PHD 33 kDa phototransducing protein MEKA protein
Homo sapiens Human
Zinc finger HIT domain containing protein 1 Cyclin G1 binding
protein 1 Homo sapiens Human
Zinc finger CCHC type and RNA binding motif containing protein 1
U11 U12 snRNP 31 kDa protein U11 U12 31K Homo sapiens Human
4
161
161
161
369
369
369
643
477
477
510
510
503
503
358
358
856
856
854
854
576
576
554
554
702
702
845
879
921
151
1
585
586
587
588
2
1.37
1.37
1.37
1.36
589
1.35
590
1.35
591
1.34
592
1.34
593
1.33
594
1.33
595
1.33
596
597
1.30
1.29
598
1.29
599
1.29
600
1.26
601
1.26
602
1.24
603
1.22
604
605
1.22
1.21
606
607
608
609
1.20
1.20
1.20
1.19
610
1.17
611
1.17
3
Bcl-2-modifying factor Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Chondroitin sulfate glucuronyltransferase EC 2 4 1 226 N acetylgalactosaminyl proteoglycan 3 beta glucuronosyltransferase Chondroitin glucuronyltransferase II CSGlcA T Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153 153
kDa nucleoporin Homo sapiens Human
Uncharacterized protein C2orf21 Homo sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing
protein 21 Homo sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing
protein 21 Homo sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing
protein 21 Homo sapiens Human
Keratin, type I cytoskeletal 9 Cytokeratin 9 CK 9 Keratin 9 K9 Homo sapiens Human
Keratin, type I cytoskeletal 9 Cytokeratin 9 CK 9 Keratin 9 K9 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens
Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo sapiens Human
Glycine cleavage system H protein mitochondrial precursor Homo
sapiens Human
Putative uncharacterized protein C10orf130 Homo sapiens Human
Putative uncharacterized protein C10orf130 Homo sapiens Human
Putative uncharacterized protein C10orf130 Homo sapiens Human
Inositol-pentakisphosphate 2 kinase EC 2 7 1 158 Inositol 1 3 4 5 6
pentakisphosphate 2 kinase Ins 1 3 4 5 6 P5 2 kinase InsP5 2 kinase
IPK1 homolog Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
4
383
383
383
605
349
349
496
496
493
493
493
471
454
454
454
524
524
551
674
674
819
357
357
357
928
333
333
152
1
612
2
1.17
613
1.17
614
1.17
615
616
617
1.15
1.15
1.14
618
1.13
619
1.12
620
1.12
621
1.11
622
1.11
623
1.11
624
1.11
625
1.09
626
627
628
629
630
1.08
1.07
1.07
1.07
1.06
631
1.05
632
1.05
633
1.04
634
1.03
635
1.03
3
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly
factor 1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Vacuolar protein sorting associated protein 25 hVps25 ELL associated protein of 20 kDa Dermal papilla derived protein 9 Homo
sapiens Human
Chromaffin granule amine transporter Vesicular amine transporter 1
VAT1 Solute carrier family 18 member 1 Homo sapiens Human
Cytochrome c oxidase polypeptide 8 isoform 3 mitochondrial precursor
EC 1 9 3 1 Cytochrome c oxidase polypeptide VIII isoform 3 Cytochrome c oxidase subunit 8 3 COX VIII 3 Homo sapiens Human
Cytochrome c oxidase polypeptide 8 isoform 3 mitochondrial precursor
EC 1 9 3 1 Cytochrome c oxidase polypeptide VIII isoform 3 Cytochrome c oxidase subunit 8 3 COX VIII 3 Homo sapiens Human
Glutaryl-CoA dehydrogenase mitochondrial precursor EC 1 3 99 7
GCD Homo sapiens Human
Glutaryl-CoA dehydrogenase mitochondrial precursor EC 1 3 99 7
GCD Homo sapiens Human
Glutaryl-CoA dehydrogenase mitochondrial precursor EC 1 3 99 7
GCD Homo sapiens Human
Glutaryl-CoA dehydrogenase mitochondrial precursor EC 1 3 99 7
GCD Homo sapiens Human
Brix domain containing protein 2 Ribosome biogenesis protein Brix
Homo sapiens Human
Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human
Acyl-CoA-binding domain containing protein 7 Homo sapiens Human
Acyl-CoA-binding domain containing protein 7 Homo sapiens Human
Acyl-CoA-binding domain containing protein 7 Homo sapiens Human
Probable U3 small nucleolar RNA associated protein 11 U3 snoRNA
associated protein 11 UTP11 like protein Homo sapiens Human
Rab GDP dissociation inhibitor alpha Rab GDI alpha Guanosine
diphosphate dissociation inhibitor 1 GDI 1 XAP 4 Oligophrenin 2
Homo sapiens Human
Rab GDP dissociation inhibitor alpha Rab GDI alpha Guanosine
diphosphate dissociation inhibitor 1 GDI 1 XAP 4 Oligophrenin 2
Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
4
333
333
333
314
314
478
810
863
863
734
734
734
734
985
527
686
686
686
704
568
568
458
556
556
153
1
636
2
1.01
637
638
639
640
1.00
0.99
0.99
0.98
641
0.97
642
0.97
643
0.96
644
0.96
645
0.94
646
647
648
649
650
651
0.90
0.89
0.89
0.89
0.88
0.82
652
653
654
655
0.79
0.78
0.75
0.73
656
0.73
657
658
659
0.70
0.70
0.69
660
0.68
661
0.68
662
0.64
663
0.64
664
0.62
3
Vacuolar protein sorting associated protein 25 hVps25 ELL associated protein of 20 kDa Dermal papilla derived protein 9 Homo
sapiens Human
Uncharacterized protein C14orf112 precursor Homo sapiens Human
Nucleolar protein 66 hsNO66 Homo sapiens Human
Nucleolar protein 66 hsNO66 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator of
Rho dependent signaling STARS Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator of
Rho dependent signaling STARS Homo sapiens Human
26S proteasome associated UCH37 interacting protein 1 X linked
protein STS1769 Homo sapiens Human
26S proteasome associated UCH37 interacting protein 1 X linked
protein STS1769 Homo sapiens Human
26S proteasome non ATPase regulatory subunit 14 26S proteasome
regulatory subunit rpn11 26S proteasome associated PAD1 homolog
1 Homo sapiens Human
Transmembrane protein 78 Homo sapiens Human
REST corepressor 3 Homo sapiens Human
REST corepressor 3 Homo sapiens Human
REST corepressor 3 Homo sapiens Human
Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human
Rho guanine nucleotide exchange factor 5 Guanine nucleotide regulatory protein TIM Oncogene TIM p60 TIM Transforming immortalized mammary oncogene Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Coiled-coil domain containing protein 25 Homo sapiens Human
Lysozyme-like protein 4 precursor Homo sapiens Human
UNC93 homolog A UNC 93A protein HmUNC 93A Homo sapiens
Human
UNC93 homolog A UNC 93A protein HmUNC 93A Homo sapiens
Human
Protein mago nashi homolog Homo sapiens Human
Protein mago nashi homolog Homo sapiens Human
HLA class II histocompatibility antigen DM beta chain precursor
MHC class II antigen DMB Homo sapiens Human
CD302 antigen precursor C type lectin domain family 13 member A
C type lectin BIMLEC Type I transmembrane C type lectin receptor
DCL 1 Homo sapiens Human
CD302 antigen precursor C type lectin domain family 13 member A
C type lectin BIMLEC Type I transmembrane C type lectin receptor
DCL 1 Homo sapiens Human
Probable RNA binding protein 18 RNA binding motif protein 18
Homo sapiens Human
Probable RNA binding protein 18 RNA binding motif protein 18
Homo sapiens Human
Matrix metalloproteinase 19 precursor EC 3 4 24 MMP 19 Matrix
metalloproteinase RASI MMP 18 Homo sapiens Human
4
475
822
481
481
721
501
501
837
837
774
861
441
441
441
539
596
972
876
462
792
792
668
668
511
799
799
785
785
981
154
1
665
666
667
668
2
0.60
0.58
0.58
0.55
669
0.54
670
0.53
671
0.53
672
0.53
673
674
675
0.52
0.51
0.50
676
0.49
677
678
0.46
0.41
679
0.41
680
681
0.37
0.36
3
Protein yippee like 4 Homo sapiens Human
Leucine-rich repeat containing protein 51 Homo sapiens Human
Leucine-rich repeat containing protein 51 Homo sapiens Human
HLA class II histocompatibility antigen DM beta chain precursor
MHC class II antigen DMB Homo sapiens Human
GTP-binding protein Di Ras1 Distinct subgroup of the Ras family
member 1 Ras related inhibitor of cell growth Rig protein Small
GTP binding tumor suppressor 1 Homo sapiens Human
Taste receptor type 2 member 42 T2R42 T2R55 Homo sapiens
Human
Taste receptor type 2 member 42 T2R42 T2R55 Homo sapiens
Human
Taste receptor type 2 member 42 T2R42 T2R55 Homo sapiens
Human
Uncharacterized protein C21orf59Homo sapiens Human
Uncharacterized protein C16orf53 Homo sapiens Human
Immunoglobulin superfamily member 8 precursor CD81 partner 3
Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes
associated transmembrane protein 4 KCT 4 LIR D1 CD316 antigen
Homo sapiens Human
B-lymphocyte antigen CD19 precursor Differentiation antigen CD19
B lymphocyte surface antigen B4 Leu 12 Homo sapiens Human
Uncharacterized protein C20orf197 Homo sapiens Human
Cysteine-rich protein 3 CRP3 Chromosome 6 LIM domain only
protein h6LIMo Homo sapiens Human
Cysteine-rich protein 3 CRP3 Chromosome 6 LIM domain only
protein h6LIMo Homo sapiens Human
Putative RNA methylase C6orf75 EC 2 1 1 Homo sapiens Human
Apolipoprotein F precursor Apo F Lipid transfer inhibitor protein
LTIP Homo sapiens Human
4
694
775
775
500
772
803
803
803
894
549
502
852
860
793
793
823
802
155
Ɍɚɛɥɢɰɚ 2
ȼɟɪɨɹɬɧɨɫɬɶ
ʋ ɩ/ɩ ɫɨɜɩɚɞɟɧɢɹ
(%)
1
2
1
2
100.00
76.56
3
47.89
4
5
38.11
34.16
6
7
32.98
31.08
8
9
10
11
27.09
17.54
15.46
15.37
12
15.07
13
14.41
14
15
16
14.15
14.03
13.59
17
13.44
18
13.38
19
20
12.58
12.49
21
12.03
22
23
24
25
11.65
11.59
11.54
11.50
ID ɛɟɥɤɨɜ ɞɥɹ CD34+ȽɋɄ (1-ɹ ɮɪɚɤɰɢɹ, 2-ɹ ɩɨɜɬɨɪɧɨɫɬɶ)
ɇɨɦɟɪ
ɩɹɬɧɚ
3
4
HEAT repeat containing protein 2 Homo sapiens Human
Zinc finger and BTB domain containing protein 41 Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens
Human
Toll-like receptor 8 precursor CD288 antigen Homo sapiens Human
Hemoglobin subunit beta Hemoglobin beta chain Beta globin
Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens
Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens
Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Rho guanine nucleotide exchange factor 5 Guanine nucleotide
regulatory protein TIM Oncogene TIM p60 TIM Transforming
immortalized mammary oncogene Homo sapiens Human
Hemoglobin subunit gamma 1 Hemoglobin gamma 1 chain
Gamma 1 globin Hemoglobin gamma A chain Hb F Agamma
Homo sapiens Human
Metalloproteinase inhibitor 2 precursor TIMP 2 Tissue inhibitor
of metalloproteinases 2 CSC 21K Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Cathepsin L2 precursor EC 3 4 22 43 Cathepsin V Cathepsin U
Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
973
1497
1185
994
895
691
467
1487
1102
376
1212
1389
373
1402
1158
1457
1276
828
655
1016
252
1083
1132
426
1249
156
1
2
3
4
26
27
28
29
30
31
32
33
34
35
36
37
10.87
10.80
10.75
10.10
10.07
10.03
9.94
9.92
9.77
9.44
9.21
9.15
351
1046
1476
1070
1015
334
1183
548
1078
419
1520
1482
38
39
40
41
42
43
44
9.03
8.92
8.84
8.84
8.72
8.58
8.54
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
7.97
7.87
7.84
7.84
7.82
7.80
7.71
7.66
7.66
7.57
7.55
7.50
7.44
7.37
7.25
7.17
7.07
7.07
6.99
6.97
65
6.97
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Complement component C8 alpha chain precursor Complement
component 8 subunit alpha Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Calcium/calmodulin-dependent protein kinase kinase 1 EC 2 7
11 17 Calcium calmodulin dependent protein kinase kinase
alpha CaM kinase kinase alpha CaM KK alpha CaMKK alpha
CaMKK 1 CaM kinase IV kinase Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Zinc finger protein 225 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
479
1310
377
377
1035
1145
1395
1062
647
1163
1163
1379
1114
763
428
428
1157
1019
352
805
1147
627
267
718
718
372
1136
1136
157
1
2
3
4
66
67
68
6.83
6.79
6.64
1079
1044
1366
69
70
6.53
6.44
71
72
73
74
6.40
6.30
6.21
6.20
75
6.18
76
77
6.16
6.12
78
6.04
79
6.03
80
81
82
5.92
5.91
5.86
83
5.85
84
5.81
85
5.71
86
5.64
87
88
89
90
5.58
5.55
5.55
5.52
91
5.50
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Transmembrane protein 106B Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Hemoglobin subunit gamma 1 Hemoglobin gamma 1 chain
Gamma 1 globin Hemoglobin gamma A chain Hb F Agamma
Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens
Human
Keratin-associated protein 21 2 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen
97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Short palate lung and nasal epithelium carcinoma associated
protein 2 precursor Parotid secretory protein PSP Homo sapiens
Human
T-cell leukemia translocation associated gene protein Homo
sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
WAP four disulfide core domain protein 1 precursor Prostate
stromal protein ps20 ps20 growth inhibitor Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
1173
578
466
1116
531
1272
1196
1126
1278
187
504
523
1392
702
1112
378
1398
614
1060
1106
1106
481
1337
158
1
2
3
4
92
93
94
95
96
5.45
5.43
5.41
5.37
5.33
618
1156
1608
329
1087
97
5.30
98
5.24
99
5.24
100
5.23
101
102
103
104
105
106
107
108
5.21
5.20
5.18
5.18
5.16
5.16
5.12
5.09
109
5.08
110
5.08
111
112
5.05
4.94
113
114
4.87
4.86
115
116
117
118
119
120
121
122
123
124
4.83
4.77
4.73
4.70
4.67
4.67
4.63
4.61
4.59
4.51
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens
Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
REST corepressor 3 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Zinc finger and BTB domain containing protein 41 Homo sapiens Human
Zinc finger and BTB domain containing protein 41 Homo sapiens Human
E3
WAP four disulfide core domain protein 1 precursor Prostate
stromal protein ps20 ps20 growth inhibitor Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
1400
1007
1007
1160
1168
669
1036
1036
1013
1013
1201
1352
1089
1089
1071
1282
1138
602
721
766
315
1148
1003
1003
1376
1105
429
1135
159
1
2
3
4
125
4.50
1023
126
127
128
4.44
4.43
4.41
129
4.41
130
4.36
131
4.33
132
133
134
135
136
137
4.31
4.31
4.30
4.29
4.27
4.23
138
139
140
141
4.22
4.22
4.22
4.19
142
143
144
145
4.17
4.16
4.15
4.14
146
147
4.07
4.03
148
3.99
149
150
151
152
3.98
3.98
3.93
3.89
153
154
3.88
3.87
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human
G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Late cornified envelope protein 3C Late envelope protein 15
Small proline rich like epidermal differentiation complex protein
3A Homo sapiens Human
SOX-12 protein SOX 22 protein Homo sapiens Human
SOX-12 protein SOX 22 protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Taste receptor type 2 member 4 T2R4 Homo sapiens Human
Taste receptor type 2 member 4 T2R4 Homo sapiens Human
Taste receptor type 2 member 4 T2R4 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Cullin-4B CUL 4B Homo sapiens Human
Cathepsin E precursor EC 3 4 23 34 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Ly6/PLAUR domain containing protein 3 precursor GPI anchored metastasis associated protein C4 4A homolog Matrigel
induced gene C4 protein MIG C4 Homo sapiens Human
Cullin-4B CUL 4B Homo sapiens Human
Growth/differentiation factor 7 precursor GDF 7 Homo sapiens
Human
Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo
sapiens Human
Actin, cytoplasmic 2 Gamma actin Homo sapiens Human
Actin, cytoplasmic 2 Gamma actin Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Zinc finger protein 225 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
521
760
582
582
810
754
664
664
635
1109
775
1184
826
826
826
725
738
815
743
546
704
822
225
938
938
505
1014
1188
497
160
1
2
3
4
155
3.86
791
156
3.86
157
3.86
158
159
160
161
162
3.84
3.84
3.84
3.84
3.83
163
3.83
164
3.82
165
3.81
166
3.81
167
3.80
168
169
170
171
172
3.79
3.78
3.77
3.77
3.73
173
3.66
174
3.66
175
176
3.65
3.60
177
3.59
178
3.58
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Taste receptor type 2 member 4 T2R4 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20
Homo sapiens Human
Kinesin-like protein KIF3A Microtubule plus end directed kinesin motor 3A Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
791
791
321
321
321
321
543
543
507
807
807
1194
992
1081
355
355
486
755
755
1498
1429
1367
514
161
1
2
3
4
179
3.57
601
180
181
182
183
184
185
186
3.56
3.56
3.55
3.54
3.54
3.54
3.52
187
3.49
188
3.45
189
3.44
190
3.44
191
3.39
192
3.39
193
194
195
196
3.38
3.36
3.36
3.33
197
198
3.32
3.29
199
3.29
200
201
202
3.28
3.28
3.27
203
3.26
204
3.24
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Integrin-linked protein kinase EC 2 7 11 1 ILK 1 ILK 2 59 kDa
serine threonine protein kinase p59ILK Homo sapiens Human
Integrin-linked protein kinase EC 2 7 11 1 ILK 1 ILK 2 59 kDa
serine threonine protein kinase p59ILK Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Zinc finger protein 225 Homo sapiens Human
Zinc finger protein 225 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Late cornified envelope protein 3C Late envelope protein 15
Small proline rich like epidermal differentiation complex protein
3A Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
650
650
1299
415
415
415
1432
1217
552
797
797
519
519
488
787
787
804
1027
1012
1012
462
462
1403
1248
513
162
1
2
3
4
205
3.22
1100
206
3.20
207
3.18
208
3.18
209
3.16
210
211
3.10
3.09
212
3.08
213
3.08
214
215
216
3.07
3.07
3.06
217
3.03
218
219
220
3.01
2.99
2.96
221
222
2.94
2.92
223
2.90
224
2.90
225
226
227
228
2.89
2.88
2.85
2.84
Protein S100 A13 S100 calcium binding protein A13 Homo
sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Sororin Cell division cycle associated protein 5 p35 Homo sapiens Human
Sororin Cell division cycle associated protein 5 p35 Homo sapiens Human
Late cornified envelope protein 3C Late envelope protein 15
Small proline rich like epidermal differentiation complex protein
3A Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20
Homo sapiens Human
B-lymphocyte antigen CD19 precursor Differentiation antigen
CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens
Human
B-lymphocyte antigen CD19 precursor Differentiation antigen
CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens
Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Uncharacterized protein C1orf210 Homo sapiens Human
Transmembrane protein 9B precursor Homo sapiens Human
Zinc finger and BTB domain containing protein 41 Homo sapiens Human
Component of gems 4 Gemin 4 p97 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Serpin A12 precursor Visceral adipose specific serpin Visceral
adipose tissue derived serine protease inhibitor Vaspin OL 64
Homo sapiens Human
Serpin A12 precursor Visceral adipose specific serpin Visceral
adipose tissue derived serine protease inhibitor Vaspin OL 64
Homo sapiens Human
Cathepsin E precursor EC 3 4 23 34 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
452
1077
1077
1242
389
527
856
856
757
757
802
499
698
1370
625
1252
789
941
941
873
1486
541
1161
163
1
2
3
4
229
230
231
232
2.84
2.83
2.77
2.75
1161
817
657
1263
233
234
235
236
2.74
2.74
2.74
2.70
237
2.70
238
2.70
239
240
2.66
2.65
241
2.64
242
2.64
243
2.64
244
245
2.59
2.58
246
2.57
247
2.57
248
2.55
249
2.52
250
2.51
251
2.49
252
2.49
Keratin-associated protein 21 2 Homo sapiens Human
Melanocortin receptor 4 MC4 R Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo
sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Calcium/calmodulin-dependent protein kinase kinase 1 EC 2 7
11 17 Calcium calmodulin dependent protein kinase kinase
alpha CaM kinase kinase alpha CaM KK alpha CaMKK alpha
CaMKK 1 CaM kinase IV kinase Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Prolargin precursor Proline arginine rich end leucine rich repeat
protein Homo sapiens Human
Late cornified envelope protein 3C Late envelope protein 15
Small proline rich like epidermal differentiation complex protein
3A Homo sapiens Human
Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo
sapiens Human
Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo
sapiens Human
501
501
501
597
597
597
1049
645
534
534
534
1410
1259
800
800
232
604
692
772
772
164
1
2
3
4
253
254
255
256
257
2.47
2.47
2.47
2.44
2.43
948
948
948
1339
453
258
2.43
259
2.42
260
2.41
261
2.41
262
263
264
2.38
2.35
2.34
265
2.34
266
2.33
267
2.32
268
269
270
271
272
273
2.28
2.27
2.27
2.26
2.26
2.25
274
2.20
275
2.20
276
2.18
Asc-type amino acid transporter 1 Asc 1 Homo sapiens Human
Asc-type amino acid transporter 1 Asc 1 Homo sapiens Human
Asc-type amino acid transporter 1 Asc 1 Homo sapiens Human
UPF0193 protein EVG1 Homo sapiens Human
Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo
sapiens Human
Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo
sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Calcium/calmodulin-dependent protein kinase kinase 1 EC 2 7
11 17 Calcium calmodulin dependent protein kinase kinase
alpha CaM kinase kinase alpha CaM KK alpha CaMKK alpha
CaMKK 1 CaM kinase IV kinase Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Angiopoietin-1 precursor ANG 1 Homo sapiens Human
Tenascin-N precursor TN N Homo sapiens Human
Tenascin-N precursor TN N Homo sapiens Human
Protein FAM23B Homo sapiens Human
Protein FAM23B Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
453
549
330
330
1068
745
323
323
1031
605
806
1092
1092
653
653
574
540
540
811
165
1
2
3
4
277
2.18
811
278
279
280
281
2.17
2.17
2.15
2.14
282
2.11
283
2.11
284
2.11
285
2.10
286
2.10
287
2.10
288
2.09
289
2.09
290
291
292
293
2.07
2.07
2.06
2.05
294
2.05
295
296
2.04
2.03
297
2.03
298
299
2.02
2.01
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Late cornified envelope protein 3C Late envelope protein 15
Small proline rich like epidermal differentiation complex protein
3A Homo sapiens Human
Late cornified envelope protein 3C Late envelope protein 15
Small proline rich like epidermal differentiation complex protein
3A Homo sapiens Human
Late cornified envelope protein 3C Late envelope protein 15
Small proline rich like epidermal differentiation complex protein
3A Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Beta-defensin 131 precursor Defensin beta 131 Beta defensin 31
DEFB 31 Homo sapiens Human
Beta-defensin 131 precursor Defensin beta 131 Beta defensin 31
DEFB 31 Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo
sapiens Human
458
458
649
1154
559
559
559
544
544
544
599
599
468
468
622
1190
1190
444
734
734
978
694
166
1
2
300
2.01
301
302
2.00
1.98
303
1.96
304
1.96
305
306
1.95
1.93
307
1.93
308
1.92
309
1.91
310
1.91
311
1.91
312
1.90
313
1.90
314
1.90
315
1.83
316
1.83
317
1.83
318
1.82
319
1.82
320
1.81
321
323
1.80
1.76
3
4
Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo
694
sapiens Human
Transmembrane protein 106B Homo sapiens Human
736
Segment polarity protein dishevelled homolog DVL 3 Dishe603
velled 3 DSH homolog 3 Homo sapiens Human
Hepatocyte nuclear factor 6 HNF 6 One cut domain family
819
member 1 Homo sapiens Human
Hepatocyte nuclear factor 6 HNF 6 One cut domain family
819
member 1 Homo sapiens Human
UPF0184 protein C9orf16 EST00098 Homo sapiens Human
863
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
611
sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
611
sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 545
protein Atrophin 1 related protein Homo sapiens Human
Sorting nexin 18 Sorting nexin associated Golgi protein 1 SH3
705
and PX domain containing protein 3B Homo sapiens Human
Sorting nexin 18 Sorting nexin associated Golgi protein 1 SH3
705
and PX domain containing protein 3B Homo sapiens Human
Sorting nexin 18 Sorting nexin associated Golgi protein 1 SH3
705
and PX domain containing protein 3B Homo sapiens Human
Cementoblastoma-derived protein 1 Cementum protein 23 CP
1073
23 Homo sapiens Human
Cementoblastoma-derived protein 1 Cementum protein 23 CP
1073
23 Homo sapiens Human
Cementoblastoma-derived protein 1 Cementum protein 23 CP
1073
23 Homo sapiens Human
B-lymphocyte antigen CD19 precursor Differentiation antigen
685
CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens
Human
B-lymphocyte antigen CD19 precursor Differentiation antigen
685
CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens
Human
B-lymphocyte antigen CD19 precursor Differentiation antigen
685
CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens
Human
Prostate, ovary testis expressed protein on chromosome 14 Ho821
mo sapiens Human
Prostate, ovary testis expressed protein on chromosome 14 Ho821
mo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like 608
protein Atrophin 1 related protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
638
Complex I intermediate associated protein 30 mitochondrial
584
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
167
1
2
3
4
324
1.75
756
325
1.73
326
327
328
1.72
1.72
1.67
329
1.65
330
1.65
331
332
333
334
335
336
337
338
339
1.64
1.64
1.63
1.63
1.62
1.62
1.60
1.60
1.59
340
1.59
341
1.59
342
1.59
344
345
346
1.57
1.57
1.55
347
1.54
348
1.54
349
1.54
350
1.52
351
1.50
352
1.50
Late cornified envelope protein 3C Late envelope protein 15
Small proline rich like epidermal differentiation complex protein
3A Homo sapiens Human
Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo
sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
B-lymphocyte antigen CD19 precursor Differentiation antigen
CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens
Human
Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo
sapiens Human
Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo
sapiens Human
L-myc-1 proto oncogene protein Homo sapiens Human
L-myc-1 proto oncogene protein Homo sapiens Human
Sex comb on midleg like protein 1 Homo sapiens Human
Sex comb on midleg like protein 1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Uncharacterized protein KIAA0280 Homo sapiens Human
Uncharacterized protein KIAA0280 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
619
1320
1320
965
425
425
690
690
931
931
796
796
937
937
500
500
500
500
1243
1243
454
792
792
792
1435
547
547
168
1
2
3
4
353
1.48
829
354
1.48
355
1.48
356
1.47
357
358
359
1.46
1.46
1.45
360
1.45
361
1.42
362
1.42
363
364
365
1.41
1.41
1.40
366
1.39
367
1.39
368
369
1.38
1.36
370
1.35
371
372
373
1.32
1.32
1.31
374
1.31
375
1.30
Metalloproteinase inhibitor 2 precursor TIMP 2 Tissue inhibitor
of metalloproteinases 2 CSC 21K Homo sapiens Human
Metalloproteinase inhibitor 2 precursor TIMP 2 Tissue inhibitor
of metalloproteinases 2 CSC 21K Homo sapiens Human
Metalloproteinase inhibitor 2 precursor TIMP 2 Tissue inhibitor
of metalloproteinases 2 CSC 21K Homo sapiens Human
Bactericidal/permeability-increasing protein like 2 precursor
Homo sapiens Human
Transmembrane protein 39A Homo sapiens Human
Transmembrane protein 39A Homo sapiens Human
Chromaffin granule amine transporter Vesicular amine transporter 1 VAT1 Solute carrier family 18 member 1 Homo sapiens
Human
Chromaffin granule amine transporter Vesicular amine transporter 1 VAT1 Solute carrier family 18 member 1 Homo sapiens
Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
NADH-ubiquinone oxidoreductase chain 1 EC 1 6 5 3 NADH
dehydrogenase subunit 1 Homo sapiens Human
Late cornified envelope protein 3C Late envelope protein 15
Small proline rich like epidermal differentiation complex protein
3A Homo sapiens Human
Late cornified envelope protein 3C Late envelope protein 15
Small proline rich like epidermal differentiation complex protein
3A Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Late cornified envelope protein 3C Late envelope protein 15
Small proline rich like epidermal differentiation complex protein
3A Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Zinc finger protein 350 Zinc finger protein ZBRK1 Zinc finger
and BRCA1 interacting protein with a KRAB domain 1 KRAB
zinc finger protein ZFQR Homo sapiens Human
829
829
1294
427
427
1076
1076
509
509
722
722
855
777
777
1098
482
394
726
726
577
577
830
169
1
2
3
4
376
1.30
830
377
1.30
378
1.29
379
1.28
380
1.27
381
382
383
384
385
386
1.26
1.26
1.25
1.22
1.20
1.19
387
1.16
388
1.16
389
1.14
390
1.14
391
1.12
392
1.12
393
1.12
394
1.10
395
1.10
396
397
398
1.09
1.08
1.05
Zinc finger protein 350 Zinc finger protein ZBRK1 Zinc finger
and BRCA1 interacting protein with a KRAB domain 1 KRAB
zinc finger protein ZFQR Homo sapiens Human
Zinc finger protein 350 Zinc finger protein ZBRK1 Zinc finger
and BRCA1 interacting protein with a KRAB domain 1 KRAB
zinc finger protein ZFQR Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Replication protein A 14 kDa subunit RP A RF A Replication
factor A protein 3 p14 Homo sapiens Human
Collagen alpha 1 VIII chain precursor Endothelial collagen
Homo sapiens Human
40S ribosomal protein S29 Homo sapiens Human
40S ribosomal protein S29 Homo sapiens Human
Optic atrophy 3 protein Homo sapiens Human
Transmembrane protein 78 Homo sapiens Human
C4b-binding protein beta chain precursor Homo sapiens Human
Uncharacterized protein C20orf54 precursor Homo sapiens
Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Zinc finger HIT domain containing protein 1 Cyclin G1 binding
protein 1 Homo sapiens Human
Zinc finger HIT domain containing protein 1 Cyclin G1 binding
protein 1 Homo sapiens Human
Zinc finger HIT domain containing protein 1 Cyclin G1 binding
protein 1 Homo sapiens Human
Metalloproteinase inhibitor 2 precursor TIMP 2 Tissue inhibitor
of metalloproteinases 2 CSC 21K Homo sapiens Human
Metalloproteinase inhibitor 2 precursor TIMP 2 Tissue inhibitor
of metalloproteinases 2 CSC 21K Homo sapiens Human
UPF0184 protein C9orf16 EST00098 Homo sapiens Human
Melanocortin receptor 4 MC4 R Homo sapiens Human
Epididymal-specific lipocalin 9 precursor MUP like lipocalin
Homo sapiens Human
830
406
678
1095
1055
1055
1304
961
857
980
489
489
626
626
684
684
684
853
853
974
982
957
170
1
2
3
4
399
1.04
823
400
1.04
401
1.04
402
1.04
403
1.03
404
1.03
405
1.00
406
1.00
407
0.97
408
0.97
409
410
411
412
0.96
0.96
0.96
0.95
413
0.95
414
0.94
415
0.94
416
0.94
417
0.93
418
0.93
Hemoglobin subunit epsilon Hemoglobin epsilon chain Epsilon
globin Homo sapiens Human
Hemoglobin subunit epsilon Hemoglobin epsilon chain Epsilon
globin Homo sapiens Human
Hemoglobin subunit epsilon Hemoglobin epsilon chain Epsilon
globin Homo sapiens Human
Hemoglobin subunit epsilon Hemoglobin epsilon chain Epsilon
globin Homo sapiens Human
Cardiotrophin-like cytokine factor 1 precursor B cell stimulating
factor 3 BSF 3 Novel neurotrophin 1 NNT 1 Homo sapiens
Human
Cardiotrophin-like cytokine factor 1 precursor B cell stimulating
factor 3 BSF 3 Novel neurotrophin 1 NNT 1 Homo sapiens
Human
NACHT, LRR and PYD containing protein 11 PYRIN containing APAF1 like protein 6 Nucleotide binding oligomerization
domain protein 17 Homo sapiens Human
NACHT, LRR and PYD containing protein 11 PYRIN containing APAF1 like protein 6 Nucleotide binding oligomerization
domain protein 17 Homo sapiens Human
Beta-defensin 131 precursor Defensin beta 131 Beta defensin 31
DEFB 31 Homo sapiens Human
Beta-defensin 131 precursor Defensin beta 131 Beta defensin 31
DEFB 31 Homo sapiens Human
Beta-tectorin precursor Homo sapiens Human
Beta-tectorin precursor Homo sapiens Human
Beta-tectorin precursor Homo sapiens Human
Chromaffin granule amine transporter Vesicular amine transporter 1 VAT1 Solute carrier family 18 member 1 Homo sapiens
Human
Chromaffin granule amine transporter Vesicular amine transporter 1 VAT1 Solute carrier family 18 member 1 Homo sapiens
Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1 like
protein Atrophin 1 related protein Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
823
823
823
989
989
814
814
955
955
920
920
920
716
716
587
587
587
562
562
171
1
2
419
0.93
420
421
0.91
0.89
422
0.89
423
0.89
424
0.88
425
0.86
426
0.85
427
0.84
428
0.84
429
430
0.83
0.82
431
0.82
432
0.81
433
0.79
434
435
436
437
0.78
0.78
0.78
0.77
438
0.75
439
0.75
440
0.74
441
0.74
442
0.73
3
4
Complex I intermediate associated protein 30 mitochondrial
562
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Serine/threonine-protein
911
Beta-defensin 131 precursor Defensin beta 131 Beta defensin 31 963
DEFB 31 Homo sapiens Human
Beta-defensin 131 precursor Defensin beta 131 Beta defensin 31 963
DEFB 31 Homo sapiens Human
Beta-defensin 131 precursor Defensin beta 131 Beta defensin 31 963
DEFB 31 Homo sapiens Human
Collagen alpha 1 VIII chain precursor Endothelial collagen
720
Homo sapiens Human
Apolipoprotein C III precursor Apo CIII ApoC III Homo sa862
piens Human
Growth hormone releasing hormone receptor precursor GHRH
947
receptor GRF receptor GRFR Homo sapiens Human
Glycine cleavage system H protein mitochondrial precursor
729
Homo sapiens Human
Glycine cleavage system H protein mitochondrial precursor
729
Homo sapiens Human
NEDD4
1492
B-lymphocyte antigen CD19 precursor Differentiation antigen
834
CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens
Human
B-lymphocyte antigen CD19 precursor Differentiation antigen
834
CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens
Human
Protein S100 A14 S100 calcium binding protein A14 S114
979
Homo sapiens Human
Protein S100 A14 S100 calcium binding protein A14 S114
977
Homo sapiens Human
L-myc-1 proto oncogene protein Homo sapiens Human
700
L-myc-1 proto oncogene protein Homo sapiens Human
700
L-myc-1 proto oncogene protein Homo sapiens Human
700
Relaxin-3 precursor Prorelaxin H3 Insulin like peptide INSL7
986
Insulin like peptide 7 Contains Relaxin 3 B chain Relaxin 3 A
chain Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like 510
protein Gastrointestinal secretory protein Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like 510
protein Gastrointestinal secretory protein Homo sapiens Human
Dopamine- and cAMP regulated neuronal phosphoprotein
703
DARPP 32 Homo sapiens Human
Dopamine- and cAMP regulated neuronal phosphoprotein
703
DARPP 32 Homo sapiens Human
Metalloproteinase inhibitor 2 precursor TIMP 2 Tissue inhibitor 946
of metalloproteinases 2 CSC 21K Homo sapiens Human
172
1
2
3
4
443
0.73
946
444
0.72
445
0.72
446
0.72
447
0.72
448
0.71
449
0.71
450
0.70
451
0.70
452
0.68
453
0.68
454
455
456
0.66
0.66
0.65
457
0.65
458
0.65
459
0.64
460
0.64
461
0.63
462
463
464
0.62
0.62
0.61
465
0.61
Metalloproteinase inhibitor 2 precursor TIMP 2 Tissue inhibitor
of metalloproteinases 2 CSC 21K Homo sapiens Human
Integrin-linked protein kinase EC 2 7 11 1 ILK 1 ILK 2 59 kDa
serine threonine protein kinase p59ILK Homo sapiens Human
Integrin-linked protein kinase EC 2 7 11 1 ILK 1 ILK 2 59 kDa
serine threonine protein kinase p59ILK Homo sapiens Human
Integrin-linked protein kinase EC 2 7 11 1 ILK 1 ILK 2 59 kDa
serine threonine protein kinase p59ILK Homo sapiens Human
Integrin-linked protein kinase EC 2 7 11 1 ILK 1 ILK 2 59 kDa
serine threonine protein kinase p59ILK Homo sapiens Human
Replication protein A 14 kDa subunit RP A RF A Replication
factor A protein 3 p14 Homo sapiens Human
Replication protein A 14 kDa subunit RP A RF A Replication
factor A protein 3 p14 Homo sapiens Human
B-lymphocyte antigen CD19 precursor Differentiation antigen
CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens
Human
B-lymphocyte antigen CD19 precursor Differentiation antigen
CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens
Human
Zinc finger HIT domain containing protein 1 Cyclin G1 binding
protein 1 Homo sapiens Human
Zinc finger HIT domain containing protein 1 Cyclin G1 binding
protein 1 Homo sapiens Human
Ig heavy chain V III region WEA Homo sapiens Human
Ig heavy chain V III region WEA Homo sapiens Human
P2Y purinoceptor 1 ATP receptor P2Y1 Purinergic receptor
Homo sapiens Human
P2Y purinoceptor 1 ATP receptor P2Y1 Purinergic receptor
Homo sapiens Human
P2Y purinoceptor 1 ATP receptor P2Y1 Purinergic receptor
Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen
97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen
97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human
Olfactory receptor 4D10 Olfactory receptor OR11 251 Homo
sapiens Human
Transcription factor jun D Homo sapiens Human
Transcription factor jun D Homo sapiens Human
Gamma-secretase subunit APH 1B APH 1b Aph 1beta Presenilin stabilization factor like Homo sapiens Human
Gamma-secretase subunit APH 1B APH 1b Aph 1beta Presenilin stabilization factor like Homo sapiens Human
490
490
490
490
677
677
831
831
732
732
661
661
697
697
697
390
390
1295
1000
1000
1059
1059
173
1
2
3
4
466
0.61
1059
467
468
469
470
471
472
473
0.60
0.60
0.60
0.60
0.60
0.60
0.59
474
0.58
475
0.58
476
0.58
477
0.57
478
0.57
479
0.57
480
0.56
481
0.56
482
0.56
483
484
485
0.54
0.54
0.53
486
0.52
487
0.52
488
0.52
489
0.52
490
0.52
Gamma-secretase subunit APH 1B APH 1b Aph 1beta Presenilin stabilization factor like Homo sapiens Human
RMD5 homolog B Homo sapiens Human
RMD5 homolog B Homo sapiens Human
RMD5 homolog B Homo sapiens Human
RMD5 homolog B Homo sapiens Human
RMD5 homolog B Homo sapiens Human
RMD5 homolog B Homo sapiens Human
Protein FAM19A1 precursor Chemokine like protein TAFA 1
Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Cathepsin L2 precursor EC 3 4 22 43 Cathepsin V Cathepsin U
Homo sapiens Human
Cathepsin L2 precursor EC 3 4 22 43 Cathepsin V Cathepsin U
Homo sapiens Human
Cathepsin L2 precursor EC 3 4 22 43 Cathepsin V Cathepsin U
Homo sapiens Human
Glycine cleavage system H protein mitochondrial precursor
Homo sapiens Human
Glycine cleavage system H protein mitochondrial precursor
Homo sapiens Human
Glycine cleavage system H protein mitochondrial precursor
Homo sapiens Human
UPF0184 protein C9orf16 EST00098 Homo sapiens Human
UPF0184 protein C9orf16 EST00098 Homo sapiens Human
Chromaffin granule amine transporter Vesicular amine transporter 1 VAT1 Solute carrier family 18 member 1 Homo sapiens
Human
Epididymal-specific lipocalin 6 precursor Lipocalin 5 Homo
sapiens Human
Epididymal-specific lipocalin 6 precursor Lipocalin 5 Homo
sapiens Human
Epididymal-specific lipocalin 6 precursor Lipocalin 5 Homo
sapiens Human
Epididymal-specific lipocalin 6 precursor Lipocalin 5 Homo
sapiens Human
Epididymal-specific lipocalin 6 precursor Lipocalin 5 Homo
sapiens Human
585
585
585
585
585
585
936
1181
1181
1181
369
369
369
748
748
748
864
864
687
820
820
820
820
820
174
1
2
3
4
491
0.50
689
492
0.49
493
0.49
494
0.48
495
0.48
496
0.47
497
0.47
498
0.47
499
500
0.44
0.42
501
0.42
502
0.34
503
0.31
504
0.27
505
0.23
Glycine cleavage system H protein mitochondrial precursor
Homo sapiens Human
Claudin-5 Transmembrane protein deleted in VCFS TMDVCF
Homo sapiens Human
Claudin-5 Transmembrane protein deleted in VCFS TMDVCF
Homo sapiens Human
Inositol-trisphosphate 3 kinase C EC 2 7 1 127 Inositol 1 4 5
trisphosphate 3 kinase C InsP 3 kinase C IP3K C Homo sapiens
Human
Inositol-trisphosphate 3 kinase C EC 2 7 1 127 Inositol 1 4 5
trisphosphate 3 kinase C InsP 3 kinase C IP3K C Homo sapiens
Human
Tumor necrosis factor receptor superfamily member 13C B cell
activating factor receptor BAFF receptor BAFF R BLyS receptor 3 CD268 antigen Homo sapiens Human
Tumor necrosis factor receptor superfamily member 13C B cell
activating factor receptor BAFF receptor BAFF R BLyS receptor 3 CD268 antigen Homo sapiens Human
Tumor necrosis factor receptor superfamily member 13C B cell
activating factor receptor BAFF receptor BAFF R BLyS receptor 3 CD268 antigen Homo sapiens Human
Coiled-coil domain containing protein 25 Homo sapiens Human
Glycine cleavage system H protein mitochondrial precursor
Homo sapiens Human
Glycine cleavage system H protein mitochondrial precursor
Homo sapiens Human
Leukocyte immunoglobulin like receptor subfamily A member
3 precursor Leukocyte immunoglobulin like receptor 4 LIR 4
Immunoglobulin like transcript 6 ILT 6 Monocyte inhibitory
receptor HM43 HM31 CD85e antigen Homo sapiens Human
NADH dehydrogenase ubiquinone 1 subunit C1 mitochondrial
precursor EC 1 6 5 3 EC 1 6 99 3 NADH ubiquinone oxidoreductase KFYI subunit Complex I KFYI CI KFYI Homo sapiens
Human
Olfactory receptor 11H6 Olfactory receptor OR14 35 Homo
sapiens Human
RING finger protein 185 Homo sapiens Human
699
699
671
671
886
886
886
901
747
747
812
969
711
688
175
Ɍɚɛɥɢɰɚ 3
ȼɟɪɨɹɬɧɨɫɬɶ
ʋ ɩ/ɩ ɫɨɜɩɚɞɟɧɢɹ
(%)
1
2
1
100.00
2
57.65
3
41.10
4
40.65
5
6
39.41
36.18
7
8
9
10
36.11
34.71
21.77
21.58
11
21.45
12
20.45
13
17.66
14
16.80
15
16.43
16
17
16.31
15.66
18
19
14.91
14.64
20
13.76
21
13.34
ID ɛɟɥɤɨɜ ɞɥɹ CD34+ȽɋɄ (2-ɹ ɮɪɚɤɰɢɹ, 1-ɹ ɩɨɜɬɨɪɧɨɫɬɶ)
ɇɨɦɟɪ
ɩɹɬɧɚ
3
4
Zinc finger protein 234 Zinc finger protein HZF4 Homo sapiens
Human
Tyrosine-protein phosphatase non receptor type 3 EC 3 1 3 48
Protein tyrosine phosphatase H1 PTP H1 Homo sapiens Human
Folylpolyglutamate synthase mitochondrial precursor EC 6 3 2
17 Folylpoly gamma glutamate synthetase FPGS Tetrahydrofolate synthase Tetrahydrofolylpolyglutamate synthase Homo
sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Uncharacterized protein C18orf54 precursor Homo sapiens Human
Tyrosine-protein phosphatase non receptor type 3 EC 3 1 3 48
Protein tyrosine phosphatase H1 PTP H1 Homo sapiens Human
Bcl-2-associated transcription factor 1 Btf Homo sapiens Human
Ribosomal protein L7 like 1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Bromodomain and PHD finger containing protein 3 Homo
sapiens Human
PR domain zinc finger protein 6 PR domain containing protein 6
Fragment Homo sapiens Human
Ribonuclease H2 subunit C RNase H2 subunit C Ribonuclease
HI subunit C Aicardi Goutieres syndrome 3 protein AGS3
RNase H1 small subunit Homo sapiens Human
Muscleblind-like protein 2 Muscleblind like protein like Muscleblind like protein like 39 Muscleblind like protein 1 Homo
sapiens Human
Ribonuclease H2 subunit C RNase H2 subunit C Ribonuclease
HI subunit C Aicardi Goutieres syndrome 3 protein AGS3
RNase H1 small subunit Homo sapiens Human
Tyrosine-protein phosphatase non receptor type 3 EC 3 1 3 48
Protein tyrosine phosphatase H1 PTP H1 Homo sapiens Human
Ribosomal protein L7 like 1 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Tyrosine-protein phosphatase non receptor type 3 EC 3 1 3 48
Protein tyrosine phosphatase H1 PTP H1 Homo sapiens Human
Leucine-rich repeat containing protein C22orf36 Homo sapiens
Human
Midline-1 EC 6 3 2 Tripartite motif containing protein 18 Putative transcription factor XPRF Midin RING finger protein 59
Midline 1 RING finger protein Homo sapiens Human
509
562
567
622
501
544
448
536
623
542
610
572
518
521
540
524
490
775
539
372
406
176
1
2
3
4
22
23
24
13.20
12.83
12.72
768
881
410
25
12.43
26
12.26
27
28
11.96
11.54
29
11.52
30
10.91
31
10.81
32
10.78
33
34
10.44
10.43
35
36
10.09
9.82
37
38
9.56
9.50
39
9.15
40
41
42
43
44
9.10
8.90
8.79
8.71
8.32
45
8.24
46
8.23
47
8.17
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Mitofusin-1 EC 3 6 5 Transmembrane GTPase MFN1 Fzo
homolog Homo sapiens Human
Tyrosine-protein phosphatase non receptor type 3 EC 3 1 3 48
Protein tyrosine phosphatase H1 PTP H1 Homo sapiens Human
Putative pre mRNA splicing factor ATP dependent RNA helicase DHX16 EC 3 6 1DEAH box protein 16 ATP dependent
RNA helicase 3 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
ER degradation enhancing alpha mannosidase like 1 Homo
sapiens Human
Probable phospholipid transporting ATPase IF EC 3 6 3 1 ATPase class I type 11B ATPase IR Homo sapiens Human
Killer cell immunoglobulin like receptor 2DL2 precursor MHC
class I NK cell receptor Natural killer associated transcript 6
NKAT 6 p58 natural killer cell receptor clone CL 43 p58 NK
receptor Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Uroplakin-1b Uroplakin Ib UPIb Tetraspanin 20 Tspan 20 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Alpha-internexin Alpha Inx 66 kDa neurofilament protein Neurofilament 66 NF 66 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
B-lymphocyte antigen precursor B lymphocyte surface antigen
721P Protein XE7 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Sulfite oxidase mitochondrial precursor EC 1 8 3 1 Homo sapiens Human
Protein-glutamine gamma glutamyltransferase Z EC 2 3 2 13
TGase Z TGZ TG Z Transglutaminase 7 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
ER degradation enhancing alpha mannosidase like 1 Homo
sapiens Human
Apolipoprotein-L6 Apolipoprotein L VI ApoL VI Homo sapiens Human
Midline-1 EC 6 3 2 Tripartite motif containing protein 18 Putative transcription factor XPRF Midin RING finger protein 59
Midline 1 RING finger protein Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6
tetrakisphosphate 5 kinase Homo sapiens Human
522
534
701
603
365
624
504
578
731
528
772
569
804
550
399
720
926
865
851
584
459
565
353
177
1
2
3
4
48
8.15
482
49
8.02
50
51
8.01
7.64
52
7.36
53
54
7.30
7.21
55
56
7.00
6.80
57
58
59
60
61
6.44
6.42
6.24
6.19
6.10
62
6.04
63
5.89
64
5.80
65
66
67
68
5.70
5.60
5.25
5.22
69
5.20
70
5.19
71
72
5.17
5.08
73
5.08
Probable phospholipid transporting ATPase IF EC 3 6 3 1 ATPase class I type 11B ATPase IR Homo sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing
protein 21 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
OTU domain containing protein 4 HIV 1 induced protein HIN 1
Homo sapiens Human
E3 ubiquitin protein ligase RNF19 EC 6 3 2 RING finger protein 19 Dorfin Double ring finger protein p38 protein Homo
sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Ribonuclease H2 subunit C RNase H2 subunit C Ribonuclease
HI subunit C Aicardi Goutieres syndrome 3 protein AGS3
RNase H1 small subunit Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Transferrin receptor protein 2 TfR2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Visual pigment like receptor peropsin Homo sapiens Human
Calcium-binding protein 2 CaBP2 Homo sapiens Human
Integrin-linked protein kinase EC 2 7 11 1 ILK 1 ILK 2 59 kDa
serine threonine protein kinase p59ILK Homo sapiens Human
cAMP-specific 3 5 cyclic phosphodiesterase 4D EC 3 1 4 17
DPDE3 PDE43 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Nucleoside diphosphate kinase mitochondrial precursor EC 2 7
4 6 NDP kinase mitochondrial NDK nm23 H4 Nucleoside diphosphate kinase D NDPKD Homo sapiens Human
Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Zinc finger BED domain containing protein 4 Homo sapiens Human
EMILIN-2 precursor Elastin microfibril interface located protein
2 Elastin microfibril interfacer 2 Protein FOAP 10 Homo sapiens Human
Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo
sapiens Human
Embryonic growth differentiation factor 1 precursor GDF 1
Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Zinc finger protein ZIC 4 Zinc finger protein of the cerebellum 4
Homo sapiens Human
Zinc finger protein ZIC 4 Zinc finger protein of the cerebellum 4
Homo sapiens Human
608
945
532
615
935
558
736
742
535
829
402
427
480
581
494
601
319
719
607
434
771
500
832
587
587
178
1
2
3
4
74
75
76
5.05
5.05
4.99
790
790
368
77
4.98
78
79
4.97
4.96
80
81
4.93
4.92
82
83
84
85
86
87
4.90
4.89
4.82
4.71
4.64
4.63
88
89
4.61
4.60
90
4.60
91
4.53
92
93
94
95
96
4.52
4.52
4.45
4.40
4.39
97
98
4.27
4.25
99
4.22
100
4.19
101
4.19
102
4.17
103
4.16
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Probable phospholipid transporting ATPase IF EC 3 6 3 1 ATPase class I type 11B ATPase IR Homo sapiens Human
Dysbindin domain containing protein 2 HSMNP1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Solute carrier family 2 facilitated glucose transporter member 8
Glucose transporter type 8 Glucose transporter type X1 Homo
sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Cathepsin E precursor EC 3 4 23 34 Homo sapiens Human
Dysbindin domain containing protein 2 HSMNP1 Homo sapiens Human
Uncharacterized protein C20orf62 Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6
tetrakisphosphate 5 kinase Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4 6
tetrakisphosphate 5 kinase Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Tumor
Muscleblind-like protein 2 Muscleblind like protein like Muscleblind like protein like 39 Muscleblind like protein 1 Homo
sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens
Human
B-lymphocyte antigen precursor B lymphocyte surface antigen
721P Protein XE7 Homo sapiens Human
B-lymphocyte antigen precursor B lymphocyte surface antigen
721P Protein XE7 Homo sapiens Human
Zinc finger CCHC domain containing protein 3 Homo sapiens
Human
Keratin-associated protein 21 2 Homo sapiens Human
495
872
863
747
508
834
853
954
724
684
503
571
498
498
781
491
491
786
493
756
450
473
485
426
426
379
732
179
1
2
3
4
104
4.04
585
105
4.00
106
3.97
107
108
3.96
3.95
109
110
111
112
113
3.94
3.94
3.92
3.90
3.89
114
3.85
115
116
117
3.84
3.83
3.80
118
3.72
119
120
121
3.66
3.65
3.63
122
123
124
3.62
3.58
3.53
125
126
127
3.47
3.46
3.43
128
129
3.42
3.41
130
131
3.33
3.30
Protein S100 A13 S100 calcium binding protein A13 Homo
sapiens Human
Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo
sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Killer cell immunoglobulin like receptor 2DL2 precursor MHC
class I NK cell receptor Natural killer associated transcript 6
NKAT 6 p58 natural killer cell receptor clone CL 43 p58 NK
receptor Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing
protein 21 Homo sapiens Human
Treacle protein Treacher Collins syndrome protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen
97 kDa linear IgA bullous dermatosis antigen Linear IgA disease antigen homolog LadA Homo sapiens Human
Probable phospholipid transporting ATPase IF EC 3 6 3 1 ATPase class I type 11B ATPase IR Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Retroviral-like aspartic protease 1 precursor EC 3 4 23 Skin
specific retroviral like aspartic protease Skin aspartic protease
SASPase TPA inducible aspartic proteinase like protein TAPS
Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
UPF0193 protein EVG1 Homo sapiens Human
ER degradation enhancing alpha mannosidase like 1 Homo
sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Kynureninase EC 3 7 1 3 L kynurenine hydrolase Homo sapiens
Human
Transmembrane protein 106B Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Secretagogin Homo sapiens Human
UPF0027 protein C22orf28 Homo sapiens Human
721
364
844
356
727
727
728
952
355
484
754
746
858
630
924
861
546
927
631
510
761
738
588
716
778
620
387
180
1
2
3
4
132
3.27
570
133
3.26
134
3.26
135
3.23
136
3.23
137
3.20
138
3.19
139
140
141
3.18
3.18
3.12
142
3.08
143
144
145
3.04
3.00
2.99
146
147
2.92
2.79
148
2.75
150
2.72
151
152
153
2.70
2.69
2.69
Probable RNA binding protein 18 RNA binding motif protein
18 Homo sapiens Human
Beta-1-syntrophin 59 kDa dystrophin associated protein A1
basic component 1 DAPA1B Tax interaction protein 43 TIP 43
Syntrophin 2 BSYN2 Homo sapiens Human
Beta-1-syntrophin 59 kDa dystrophin associated protein A1
basic component 1 DAPA1B Tax interaction protein 43 TIP 43
Syntrophin 2 BSYN2 Homo sapiens Human
Tumor necrosis factor receptor superfamily member EDAR
precursor Anhidrotic ectodysplasin receptor 1 Ectodysplasin A
receptor EDA A1 receptor Ectodermal dysplasia receptor
Downless homolog Homo sapiens Human
Tumor necrosis factor receptor superfamily member EDAR
precursor Anhidrotic ectodysplasin receptor 1 Ectodysplasin A
receptor EDA A1 receptor Ectodermal dysplasia receptor
Downless homolog Homo sapiens Human
Melanoma-associated antigen 1 MAGE 1 antigen Antigen MZ2
E Homo sapiens Human
Growth/differentiation factor 3 precursor GDF 3 Homo sapiens
Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Ubiquitin-associated domain containing protein 1 E3 ubiquitin
protein ligase subunit KPC2 Kip1 ubiquitination promoting
complex protein 2 Glialblastoma cell differentiation related
protein 1 Homo sapiens Human
SAM pointed domain containing Ets transcription factor Prostate derived Ets factor Prostate epithelium specific Ets transcription factor Prostate specific Ets Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Claudin-17 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Olfactory receptor 4D1 Olfactory receptor TPCR16 Homo sapiens Human
Late cornified envelope protein 3C Late envelope protein 15
Small proline rich like epidermal differentiation complex protein
3A Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Uncharacterized protein C20orf111 Homo sapiens Human
Uncharacterized protein C20orf111 Homo sapiens Human
400
400
370
370
696
594
937
937
398
576
737
744
486
436
507
394
877
616
470
470
181
1
2
3
4
154
2.66
640
155
2.60
156
2.60
157
158
2.58
2.57
159
2.52
160
2.52
161
2.49
162
163
2.47
2.43
164
2.43
165
2.42
166
2.41
167
2.37
168
2.36
169
170
2.35
2.34
171
2.33
172
2.31
173
2.30
174
2.29
175
176
177
178
2.21
2.21
2.16
2.15
179
2.15
Embryonic growth differentiation factor 1 precursor GDF 1
Homo sapiens Human
cAMP-specific 3 5 cyclic phosphodiesterase 4D EC 3 1 4 17
DPDE3 PDE43 Homo sapiens Human
cAMP-specific 3 5 cyclic phosphodiesterase 4D EC 3 1 4 17
DPDE3 PDE43 Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Embryonic growth differentiation factor 1 precursor GDF 1
Homo sapiens Human
Kallikrein-10 precursor EC 3 4 21 Protease serine like 1 Normal
epithelial cell specific 1 Homo sapiens Human
Kallikrein-10 precursor EC 3 4 21 Protease serine like 1 Normal
epithelial cell specific 1 Homo sapiens Human
Dysbindin domain containing protein 2 HSMNP1 Homo sapiens Human
Beta-1,4-galactosyltransferase
Protein S100 A13 S100 calcium binding protein A13 Homo
sapiens Human
Protein S100 A13 S100 calcium binding protein A13 Homo
sapiens Human
Protein S100 A13 S100 calcium binding protein A13 Homo
sapiens Human
Kynureninase EC 3 7 1 3 L kynurenine hydrolase Homo sapiens
Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Uroplakin-1b Uroplakin Ib UPIb Tetraspanin 20 Tspan 20 Homo sapiens Human
Matrilin-4 precursor Homo sapiens Human
Inner nuclear membrane protein Man1 LEM domain containing
protein 3 Homo sapiens Human
RNA 3 terminal phosphate cyclase EC 6 5 1 4 RNA 3 phosphate cyclase RNA cyclase Homo sapiens Human
Histidine-rich glycoprotein precursor Histidine proline rich
glycoprotein HPRG Homo sapiens Human
ER degradation enhancing alpha mannosidase like 1 Homo
sapiens Human
Kynureninase EC 3 7 1 3 L kynurenine hydrolase Homo sapiens
Human
Coiled-coil domain containing protein 8 Homo sapiens Human
Coiled-coil domain containing protein 8 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiensHuman
Spindle and kinetochore associated protein 2 Protein FAM33A
Homo sapiens Human
Spindle and kinetochore associated protein 2 Protein FAM33A
Homo sapiens Human
421
421
760
469
349
349
600
391
579
579
393
499
483
407
953
548
621
530
388
396
502
502
665
589
589
182
1
2
3
4
180
2.11
685
181
182
2.08
2.07
183
2.06
184
2.04
185
2.04
186
2.03
187
188
2.01
1.99
189
1.98
190
1.97
191
1.97
192
193
194
195
196
197
1.96
1.96
1.95
1.95
1.94
1.92
198
199
1.91
1.89
200
1.81
201
202
203
1.80
1.80
1.78
204
1.76
26S protease regulatory subunit S10B Proteasome 26S subunit
ATPase 6 Proteasome subunit p42 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Protein pellino homolog 1 Pellino 1 Pellino related intracellular
signaling molecule Homo sapiens Human
Ubiquitin-like protein 7 Ubiquitin like protein SB132 Bone
marrow stromal cell ubiquitin like protein BMSC UbP Homo
sapiens Human
Achaete-scute homolog 2 Mash2 HASH2 Homo sapiens Human
Achaete-scute homolog 2 Mash2 HASH2 Homo sapiens Human
Embryonic growth differentiation factor 1 precursor GDF 1
Homo sapiens Human
Protein FAM22G precursor Homo sapiens Human
Protein S100 A13 S100 calcium binding protein A13 Homo
sapiens Human
Protein S100 A13 S100 calcium binding protein A13 Homo
sapiens Human
Late cornified envelope protein 3C Late envelope protein 15
Small proline rich like epidermal differentiation complex protein
3A Homo sapiens Human
Late cornified envelope protein 3C Late envelope protein 15
Small proline rich like epidermal differentiation complex protein
3A Homo sapiens Human
Ras-related protein Rab 25 CATX 8 Homo sapiens Human
Ras-related protein Rab 25 CATX 8 Homo sapiens Human
Serum
Serum
Protein yippee like 4 Homo sapiens Human
Late cornified envelope protein 3C Late envelope protein 15
Small proline rich like epidermal differentiation complex protein
3A Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Muscleblind-like protein 2 Muscleblind like protein like Muscleblind like protein like 39 Muscleblind like protein 1 Homo
sapiens Human
B-lymphocyte antigen CD19 precursor Differentiation antigen
CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens
Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Synaptotagmin-15 Synaptotagmin XV SytXV Chr10Syt Homo
sapiens Human
Probable RNA binding protein 18 RNA binding motif protein
18 Homo sapiens Human
857
512
586
557
557
598
453
457
574
334
334
429
429
411
411
618
808
706
433
363
639
639
416
413
183
1
2
3
4
205
1.76
413
206
1.76
207
208
1.75
1.70
209
1.70
210
211
1.66
1.64
212
213
1.61
1.60
214
1.60
215
216
1.58
1.57
217
218
1.56
1.55
219
1.55
220
1.52
221
1.51
222
1.51
223
1.50
224
1.44
225
1.43
226
1.43
227
1.40
Probable RNA binding protein 18 RNA binding motif protein
18 Homo sapiens Human
Probable RNA binding protein 18 RNA binding motif protein
18 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
cAMP-dependent protein kinase inhibitor alpha PKI alpha
cAMP dependent protein kinase inhibitor muscle brain isoform
Homo sapiens Human
cAMP-dependent protein kinase inhibitor alpha PKI alpha
cAMP dependent protein kinase inhibitor muscle brain isoform
Homo sapiens Human
Frizzled-1 precursor Fz 1 hFz1 FzE1 Homo sapiens Human
Probable RNA binding protein 18 RNA binding motif protein
18 Homo sapiens Human
Calcium-binding protein 2 CaBP2 Homo sapiens Human
Protein S100 A13 S100 calcium binding protein A13 Homo
sapiens Human
Protein S100 A13 S100 calcium binding protein A13 Homo
sapiens Human
Transcription factor jun D Homo sapiens Human
Protein S100 A13 S100 calcium binding protein A13 Homo
sapiens Human
Uncharacterized protein KIAA0280 Homo sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing
protein 21 Homo sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing
protein 21 Homo sapiens Human
DNA polymerase subunit delta 2 EC 2 7 7 7 DNA polymerase
subunit delta p50 Homo sapiens Human
Nasal embryonic luteinizing hormone releasing hormone factor
Nasal embryonic LHRH factor Homo sapiens Human
Nasal embryonic luteinizing hormone releasing hormone factor
Nasal embryonic LHRH factor Homo sapiens Human
Chromaffin granule amine transporter Vesicular amine transporter 1 VAT1 Solute carrier family 18 member 1 Homo sapiens
Human
Epididymal-specific lipocalin 6 precursor Lipocalin 5 Homo
sapiens Human
Ly6/PLAUR domain containing protein 3 precursor GPI anchored metastasis associated protein C4 4A homolog Matrigel
induced gene C4 protein MIG C4 Homo sapiens Human
Ly6/PLAUR domain containing protein 3 precursor GPI anchored metastasis associated protein C4 4A homolog Matrigel
induced gene C4 protein MIG C4 Homo sapiens Human
Tumor necrosis factor receptor superfamily member 19 precursor Toxicity and JNK inducer TRADE Homo sapiens Human
413
948
717
717
734
529
568
384
384
595
525
690
321
321
553
446
446
641
697
481
481
566
184
1
2
3
4
228
1.40
566
229
1.39
230
1.39
231
1.38
232
1.38
233
1.37
234
1.37
235
1.36
236
1.36
237
1.35
238
1.33
239
1.30
240
1.30
241
1.29
242
243
1.28
1.27
244
1.26
245
1.24
Tumor necrosis factor receptor superfamily member 19 precursor Toxicity and JNK inducer TRADE Homo sapiens Human
UDP-N-acetylglucosamine transporter Golgi UDP GlcNAc
transporter Solute carrier family 35 member A3 Homo sapiens
Human
UDP-N-acetylglucosamine transporter Golgi UDP GlcNAc
transporter Solute carrier family 35 member A3 Homo sapiens
Human
Serine/threonine-protein kinase PLK3 EC 2 7 11 21 Polo like
kinase 3 PLK 3 Cytokine inducible serine threonine protein
kinase FGF inducible kinase Proliferation related kinase Homo
sapiens Human
Serine/threonine-protein kinase PLK3 EC 2 7 11 21 Polo like
kinase 3 PLK 3 Cytokine inducible serine threonine protein
kinase FGF inducible kinase Proliferation related kinase Homo
sapiens Human
Kynureninase EC 3 7 1 3 L kynurenine hydrolase Homo sapiens
Human
Kynureninase EC 3 7 1 3 L kynurenine hydrolase Homo sapiens
Human
B-lymphocyte antigen CD19 precursor Differentiation antigen
CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens
Human
B-lymphocyte antigen CD19 precursor Differentiation antigen
CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens
Human
R-spondin-1 precursor Roof plate specific spondin 1 hRspo1
Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
B-lymphocyte antigen CD19 precursor Differentiation antigen
CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens
Human
B-lymphocyte antigen CD19 precursor Differentiation antigen
CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens
Human
L-lactate dehydrogenase A chain EC 1 1 1 27 LDH A LDH
muscle subunit LDH M Proliferation inducing gene 19 protein
Renal carcinoma antigen NY REN 59 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Translocator protein Peripheral type benzodiazepine receptor
PBR PKBS Mitochondrial benzodiazepine receptor Homo sapiens Human
WAP four disulfide core domain protein 10A precursor Putative
protease inhibitor WAP10A Homo sapiens Human
UPF0308 protein C9orf21 Homo sapiens Human
460
460
575
575
517
517
520
520
463
496
489
489
946
933
591
691
511
185
1
2
3
4
246
247
248
1.21
1.20
1.19
408
932
506
249
1.19
250
1.19
251
1.18
252
1.17
253
1.17
254
1.14
255
256
257
1.13
1.13
1.10
258
1.10
259
1.10
260
1.09
261
1.05
262
263
264
1.02
1.02
1.01
265
1.01
266
1.01
267
1.00
268
0.99
269
0.99
DNA polymerase beta EC 2 7 7 7 EC 4 2 99 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing
protein 21 Homo sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing
protein 21 Homo sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing
protein 21 Homo sapiens Human
Tumor necrosis factor receptor superfamily member 13C B cell
activating factor receptor BAFF receptor BAFF R BLyS receptor 3 CD268 antigen Homo sapiens Human
cAMP-dependent protein kinase inhibitor alpha PKI alpha
cAMP dependent protein kinase inhibitor muscle brain isoform
Homo sapiens Human
cAMP-dependent protein kinase inhibitor alpha PKI alpha
cAMP dependent protein kinase inhibitor muscle brain isoform
Homo sapiens Human
Guanine deaminase EC 3 5 4 3 Guanase Guanine aminase Guanine aminohydrolase GAH p51 nedasin Homo sapiens Human
Uncharacterized protein C20orf62 Homo sapiens Human
Uncharacterized protein C20orf62 Homo sapiens Human
Neuronal acetylcholine receptor subunit alpha 6 precursor Homo sapiens Human
Neuronal acetylcholine receptor subunit alpha 6 precursor Homo sapiens Human
Neuronal acetylcholine receptor subunit alpha 6 precursor Homo sapiens Human
Protein S100 A13 S100 calcium binding protein A13 Homo
sapiens Human
Chitinase 3 like protein 2 precursor YKL 39 Chondrocyte protein 39 Homo sapiens Human
Beta-1,4-galactosyltransferase
Beta-1,4-galactosyltransferase
B-lymphocyte antigen precursor B lymphocyte surface antigen
721P Protein XE7 Homo sapiens Human
B-lymphocyte antigen precursor B lymphocyte surface antigen
721P Protein XE7 Homo sapiens Human
B-lymphocyte antigen precursor B lymphocyte surface antigen
721P Protein XE7 Homo sapiens Human
B-lymphocyte antigen CD19 precursor Differentiation antigen
CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens
Human
UPF0384 protein CGI 117 HBV pre S2 trans regulated protein 3
Homo sapiens Human
UPF0384 protein CGI 117 HBV pre S2 trans regulated protein 3
Homo sapiens Human
506
506
642
703
703
478
423
423
358
358
358
454
420
523
523
435
435
435
702
464
464
186
1
2
270
271
272
273
0.98
0.98
0.98
0.96
274
0.96
275
0.95
276
277
278
279
0.94
0.94
0.92
0.91
280
0.91
281
0.91
282
0.88
283
0.88
284
0.88
285
286
287
288
289
290
291
0.86
0.85
0.85
0.85
0.84
0.84
0.83
292
293
294
295
296
297
298
0.82
0.82
0.78
0.78
0.78
0.78
0.78
3
Visual pigment like receptor peropsin Homo sapiens Human
Visual pigment like receptor peropsin Homo sapiens Human
Visual pigment like receptor peropsin Homo sapiens Human
Sorting nexin 18 Sorting nexin associated Golgi protein 1 SH3
and PX domain containing protein 3B Homo sapiens Human
Sorting nexin 18 Sorting nexin associated Golgi protein 1 SH3
and PX domain containing protein 3B Homo sapiens Human
Ubiquitin-like protein 7 Ubiquitin like protein SB132 Bone
marrow stromal cell ubiquitin like protein BMSC UbP Homo
sapiens Human
UPF0327 protein C1orf151 Homo sapiens Human
UPF0327 protein C1orf151 Homo sapiens Human
Beta-tectorin precursor Homo sapiens Human
Spindle and kinetochore associated protein 2 Protein FAM33A
Homo sapiens Human
Spindle and kinetochore associated protein 2 Protein FAM33A
Homo sapiens Human
Spindle and kinetochore associated protein 2 Protein FAM33A
Homo sapiens Human
Tumor necrosis factor receptor superfamily member EDAR
precursor Anhidrotic ectodysplasin receptor 1 Ectodysplasin A
receptor EDA A1 receptor Ectodermal dysplasia receptor
Downless homolog Homo sapiens Human
Tumor necrosis factor receptor superfamily member EDAR
precursor Anhidrotic ectodysplasin receptor 1 Ectodysplasin A
receptor EDA A1 receptor Ectodermal dysplasia receptor
Downless homolog Homo sapiens Human
Tumor necrosis factor receptor superfamily member EDAR
precursor Anhidrotic ectodysplasin receptor 1 Ectodysplasin A
receptor EDA A1 receptor Ectodermal dysplasia receptor
Downless homolog Homo sapiens Human
UPF0399 protein C6orf153 Homo sapiens Human
AP-2
AP-2
AP-2
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
GTP-binding protein SAR1a COPII associated small GTPase
Homo sapiens Human
NIPA-like protein 3 Homo sapiens Human
NIPA-like protein 3 Homo sapiens Human
AP-2
AP-2
AP-2
AP-2
AP-2
4
417
417
417
683
683
774
432
432
333
419
419
419
474
474
474
629
477
477
477
345
345
458
390
390
385
385
385
385
385
187
1
2
3
4
299
300
301
0.75
0.75
0.74
389
389
590
302
0.74
303
0.74
304
0.71
305
0.70
306
0.68
307
0.67
308
0.67
309
0.66
310
0.66
311
0.63
312
313
314
315
316
317
318
0.62
0.60
0.60
0.59
0.53
0.49
0.46
319
0.45
OTU domain containing protein 6A Homo sapiens Human
OTU domain containing protein 6A Homo sapiens Human
Neuropeptide B precursor Preproprotein L7 hPPL7 Contains
Neuropeptide B 23 NPB23 hL7 Neuropeptide B 29 NPB29
hL7C Homo sapiens Human
Neuropeptide B precursor Preproprotein L7 hPPL7 Contains
Neuropeptide B 23 NPB23 hL7 Neuropeptide B 29 NPB29
hL7C Homo sapiens Human
Neuropeptide B precursor Preproprotein L7 hPPL7 Contains
Neuropeptide B 23 NPB23 hL7 Neuropeptide B 29 NPB29
hL7C Homo sapiens Human
Claudin-5 Transmembrane protein deleted in VCFS TMDVCF
Homo sapiens Human
HIG1 domain family member 1B Protein CLST 11240 Homo
sapiens Human
Phosphoglycerate kinase 1 EC 2 7 2 3 Primer recognition protein 2 PRP 2 Cell migration inducing gene 10 protein Homo
sapiens Human
B-lymphocyte antigen CD19 precursor Differentiation antigen
CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens
Human
B-lymphocyte antigen CD19 precursor Differentiation antigen
CD19 B lymphocyte surface antigen B4 Leu 12 Homo sapiens
Human
Chromaffin granule amine transporter Vesicular amine transporter 1 VAT1 Solute carrier family 18 member 1 Homo sapiens
Human
Chromaffin granule amine transporter Vesicular amine transporter 1 VAT1 Solute carrier family 18 member 1 Homo sapiens
Human
Zinc finger HIT domain containing protein 1 Cyclin G1 binding
protein 1 Homo sapiens Human
Uncharacterized protein C20orf108 Homo sapiens Human
Calcium-binding protein 3 CaBP3 Homo sapiens Human
Calcium-binding protein 3 CaBP3 Homo sapiens Human
Uncharacterized protein C14orf128 Homo sapiens Human
Ig heavy chain V III region TRO Homo sapiens Human
Putative uncharacterized protein C8orf39 Homo sapiens Human
Retroviral-like aspartic protease 1 precursor EC 3 4 23 Skin
specific retroviral like aspartic protease Skin aspartic protease
SASPase TPA inducible aspartic proteinase like protein TAPS
Homo sapiens Human
Tumor protein p73 like p73L p63 Tumor protein 63 TP63 p51
p40 Keratinocyte transcription factor KET Chronic ulcerative
stomatitis protein CUSP Homo sapiens Human
590
590
779
637
627
354
354
625
625
689
664
612
612
634
465
452
643
688
188
1
2
3
4
320
0.43
787
321
322
323
324
0.42
0.39
0.35
0.31
325
0.30
326
327
328
0.26
0.25
0.15
Autophagy-related protein 7 APG7 like Ubiquitin activating
enzyme E1 like protein hAGP7 Homo sapiens Human
Uncharacterized protein KIAA0280 Homo sapiens Human
40S ribosomal protein S29 Homo sapiens Human
Beta-1,4-galactosyltransferase
Glucocorticoid modulatory element binding protein 2 GMEB 2
Parvovirus initiation factor p79 PIF p79 DNA binding protein
p79PIF Homo sapiens Human
Zinc finger protein 148 Zinc finger DNA binding protein 89
Transcription factor ZBP 89 Homo sapiens Human
Uncharacterized protein C2orf32 Homo sapiens Human
Placenta growth factor precursor PlGF Homo sapiens Human
Mitochondrial ribosomal protein S23 S23mt MRP S23 Homo
sapiens Human
635
467
709
650
456
687
461
471
189
Ɍɚɛɥɢɰɚ 4
ȼɟɪɨɹɬɧɨɫɬɶ
ʋ ɩ/ɩ ɫɨɜɩɚɞɟɧɢɹ
(%)
1
2
1
82.94
2
82.01
3
77.06
4
69.62
5
64.63
6
64.28
7
60.10
8
53.38
9
53.27
10
11
53.24
52.80
12
50.05
13
48.92
14
15
47.46
44.57
16
42.07
17
41.31
18
19
20
38.41
38.20
37.79
21
37.60
ID ɛɟɥɤɨɜ ɞɥɹ CD34+ȽɋɄ (2-ɹ ɮɪɚɤɰɢɹ, 2-ɹ ɩɨɜɬɨɪɧɨɫɬɶ)
ɇɨɦɟɪ
ɩɹɬɧɚ
3
4
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1
CD316 antigen Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Zinc finger protein 225 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Vacuolar protein sorting associated protein 25 hVps25 ELL
associated protein of 20 kDa Dermal papilla derived protein 9
Homo sapiens Human
Cullin-3 CUL 3 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Uncharacterized protein C18orf54 precursor Homo sapiens
Human
Bcl-2-modifying factor Homo sapiens Human
Uncharacterized protein C18orf54 precursor Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Zinc finger BED domain containing protein 4 Homo sapiens
Human
12289
12354
12354
12354
12354
12354
12334
12344
12548
12576
12611
12419
12419
12419
12539
12539
12504
12324
12515
12602
12605
190
1
2
3
4
22
36.31
12490
23
35.18
24
34.54
25
33.64
26
31.87
27
28.92
28
27.46
29
25.19
30
24.98
31
24.76
32
24.00
33
23.75
34
22.57
35
21.79
36
21.75
37
21.59
38
21.48
39
20.86
40
41
20.12
20.04
42
19.72
43
44
19.48
19.44
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin
Nup153153 kDa nucleoporin Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Uncharacterized protein C18orf54 precursor Homo sapiens
Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens
Human
Vacuolar protein sorting associated protein 25 hVps25 ELL
associated protein of 20 kDa Dermal papilla derived protein 9
Homo sapiens Human
Transcription factor MafK Erythroid transcription factor NF
E2 p18 subunit Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Protein phosphatase Slingshot homolog 2 EC 3 1 3 48 EC 3 1
3 16 SSH 2L hSSH 2L Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Dihydropyridine-sensitive L type calcium channel subunits
alpha 2 delta precursor Contains L type calcium channel subunit alpha 2 L type calcium channel subunit delta Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Glial fibrillary acidic protein astrocyte GFAP Homo sapiens
Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Uncharacterized protein C21orf93 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
12490
12276
12276
12276
12276
12276
12276
12276
12276
12276
12276
12276
12276
12276
12517
12517
12484
12321
12285
12285
12285
12285
191
1
2
3
4
45
18.82
12285
46
18.59
47
18.52
48
17.87
49
17.47
50
17.18
51
17.07
52
16.15
53
16.08
54
16.05
55
15.93
56
15.50
57
15.38
58
15.34
59
15.13
60
61
14.84
14.80
62
14.71
63
14.52
64
14.43
65
14.35
Px19-like protein 25 kDa protein of relevant evolutionary and
lymphoid interest PRELI Homo sapiens Human
Uncharacterized protein C18orf54 precursor Homo sapiens
Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20
Homo sapiens Human
Zinc finger BED domain containing protein 4 Homo sapiens
Human
Uncharacterized protein C18orf54 precursor Homo sapiens
Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4
6 tetrakisphosphate 5 kinase Homo sapiens Human
F-box/LRR-repeat protein 2 F box and leucine rich repeat
protein 2 F box protein FBL2 FBL3 Homo sapiens Human
Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1
CD316 antigen Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Tyrosine-protein phosphatase non receptor type 23 EC 3 1 3
48 His domain containing protein tyrosine phosphatase HD
PTP Protein tyrosine phosphatase TD14 PTP TD14 Homo
sapiens Human
Px19-like protein 25 kDa protein of relevant evolutionary and
lymphoid interest PRELI Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Selenocysteine-specific elongation factor Elongation factor sec
Eukaryotic elongation factor selenocysteine tRNA specific
Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20
Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
12285
12285
12285
12427
12612
12555
12494
12359
12359
12433
12208
12208
12208
12208
12208
12208
12208
12208
12208
12208
192
1
2
3
4
66
14.12
12208
67
13.68
68
13.61
69
13.59
70
13.22
71
72
13.19
13.15
73
13.12
74
13.11
75
13.00
76
12.83
77
12.71
78
12.70
79
12.46
80
12.33
81
12.30
82
83
12.05
11.98
84
85
11.87
11.77
86
87
11.69
11.62
Mitochondrial intermediate peptidase mitochondrial precursor
EC 3 4 24 59 MIP Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Ubiquitin carboxyl terminal hydrolase 42 EC 3 1 2 15 Ubiquitin thioesterase 42 Ubiquitin specific processing protease 42
Deubiquitinating enzyme 42 Homo sapiens Human
Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1
CD316 antigen Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Low-density lipoprotein receptor related protein 8 precursor
Apolipoprotein E receptor 2 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Zinc finger BED domain containing protein 4 Homo sapiens
Human
Reticulon-2 Neuroendocrine specific protein like 1 NSP like
protein 1 NSPLI Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Vacuolar protein sorting associated protein 25 hVps25 ELL
associated protein of 20 kDa Dermal papilla derived protein 9
Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Zinc finger BED domain containing protein 4 Homo sapiens
Human
Killer cell immunoglobulin like receptor 2DL2 precursor
MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43
p58 NK receptor Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Complement factor H precursor H factor 1 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Probable phospholipid transporting ATPase IF EC 3 6 3 1
ATPase class I type 11B ATPase IR Homo sapiens Human
12208
12208
12208
12375
12521
12341
12514
12622
12381
12381
12381
12381
12381
12381
12381
12381
12381
12381
12381
12381
12381
193
1
2
3
4
88
89
11.48
11.34
12381
12381
90
11.28
91
11.28
92
10.93
93
10.85
94
10.79
95
10.74
96
10.53
97
10.49
98
10.44
99
10.32
100
10.14
101
10.14
102
10.03
103
9.80
104
9.66
105
106
9.57
9.45
107
9.43
108
9.33
109
9.32
Bcl-2-modifying factor Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Transcription factor MafK Erythroid transcription factor NF
E2 p18 subunit Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Olfactory receptor 4D1 Olfactory receptor TPCR16 Homo
sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Regulator of nonsense transcripts 3A Nonsense mRNA reducing factor 3A Up frameshift suppressor 3 homolog A hUpf3
Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Interphotoreceptor matrix proteoglycan 1 precursor Interphotoreceptor matrix proteoglycan of 150 kDa IPM 150 Sialoprotein
associated with cones and rods Homo sapiens Human
Reticulon-2 Neuroendocrine specific protein like 1 NSP like
protein 1 NSPLI Homo sapiens Human
Reticulon-2 Neuroendocrine specific protein like 1 NSP like
protein 1 NSPLI Homo sapiens Human
Transcription factor MafK Erythroid transcription factor NF
E2 p18 subunit Homo sapiens Human
Ubiquitin carboxyl terminal hydrolase 42 EC 3 1 2 15 Ubiquitin thioesterase 42 Ubiquitin specific processing protease 42
Deubiquitinating enzyme 42 Homo sapiens Human
Zinc finger MYM type protein 3 Zinc finger protein 261 Homo
sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
E3 ubiquitin protein ligase RNF19 EC 6 3 2 RING finger protein 19 Dorfin Double ring finger protein p38 protein Homo
sapiens Human
Mannose-binding protein C precursor MBP C MBP1 Mannan
binding protein Mannose binding lectin Homo sapiens Human
Zinc finger BED domain containing protein 4 Homo sapiens
Human
Reticulon-2 Neuroendocrine specific protein like 1 NSP like
protein 1 NSPLI Homo sapiens Human
12381
12381
12381
12381
12381
12381
12381
12381
12381
12381
12381
12381
12482
12313
12394
12459
12558
12325
12325
12325
194
1
2
3
4
110
111
9.20
9.18
12325
12325
112
9.16
113
114
8.94
8.93
115
8.93
116
8.78
117
118
119
120
121
8.69
8.62
8.56
8.44
8.40
122
8.29
123
124
8.28
8.27
125
8.22
126
127
8.07
7.96
128
129
130
131
7.87
7.75
7.75
7.69
132
7.68
133
7.55
134
7.51
135
7.46
136
7.41
Zinc finger protein 225 Homo sapiens Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Potassium voltage gated channel subfamily KQT member 5 Voltage gated potassium channel subunit Kv7 5 Potassium channel
subunit alpha KvLQT5 KQT like 5 Homo sapiens Human
Uncharacterized protein C2orf21 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Killer
RMD5 homolog B Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4
6 tetrakisphosphate 5 kinase Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Glial fibrillary acidic protein astrocyte GFAP Homo sapiens
Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Calmegin precursor Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Transcription factor MafK Erythroid transcription factor NF
E2 p18 subunit Homo sapiens Human
Suppressor of cytokine signaling 6 SOCS 6 Suppressor of
cytokine signaling 4 SOCS 4 Cytokine inducible SH2 protein
4 CIS 4 Homo sapiens Human
Aldehyde dehydrogenase dimeric NADP preferring EC 1 2 1 5
ALDH class 3 ALDHIII Homo sapiens Human
Reticulon-2 Neuroendocrine specific protein like 1 NSP like
protein 1 NSPLI Homo sapiens Human
Transcription factor MafK Erythroid transcription factor NF
E2 p18 subunit Homo sapiens Human
Fibroblast growth factor 22 precursor FGF 22 Homo sapiens
Human
12634
12634
12634
12275
12275
12254
12254
12254
12577
12607
12546
12225
12492
12357
12357
12520
12299
12470
12610
12596
12272
12272
12272
12440
12234
195
1
2
3
4
137
7.35
12234
138
7.21
139
7.17
140
7.00
141
6.96
142
6.80
143
144
6.69
6.55
145
146
6.48
6.40
147
6.38
148
6.25
149
6.07
150
6.06
151
6.06
152
6.04
153
5.98
154
5.98
155
5.93
156
5.90
157
158
159
160
161
5.89
5.84
5.83
5.78
5.76
Reticulon-2 Neuroendocrine specific protein like 1 NSP like
protein 1 NSPLI Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Uncharacterized protein C18orf54 precursor Homo sapiens
Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Fibroblast growth factor 22 precursor FGF 22 Homo sapiens
Human
Bcl-2-modifying factor Homo sapiens Human
Keratin, type I cytoskeletal 9 Cytokeratin 9 CK 9 Keratin 9 K9
Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Gamma crystallin C Gamma crystallin 2 1 Gamma crystallin 3
Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Uncharacterized protein C18orf54 precursor Homo sapiens
Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens
Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens
Human
Aldehyde dehydrogenase dimeric NADP preferring EC 1 2 1 5
ALDH class 3 ALDHIII Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Nucleolar protein 66 hsNO66 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Retinol dehydrogenase 13 EC 1 1 1 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
12345
12426
12301
12336
12336
12336
12336
12336
12336
12432
12401
12323
12442
12481
12476
12595
12538
12613
12270
12270
12410
12410
12574
12404
196
1
2
3
4
162
5.66
12404
163
5.62
164
5.52
165
5.52
166
5.49
167
168
169
170
5.41
5.40
5.39
5.37
171
5.37
172
5.35
173
5.32
174
5.25
175
5.20
176
177
5.05
5.01
178
179
180
4.99
4.96
4.95
181
182
4.93
4.88
183
4.80
184
4.79
185
4.78
Presequence protease mitochondrial precursor EC 3 4 24
hPreP Pitrilysin metalloproteinase 1 Metalloprotease 1 hMP1
Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4
6 tetrakisphosphate 5 kinase Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Nucleolar protein 66 hsNO66 Homo sapiens Human
Zinc finger protein 225 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens
Human
Putative ATP dependent RNA helicase DHX33 EC 3 6 1
DEAH box protein 33 Homo sapiens Human
Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1
CD316 antigen Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
ATP-binding cassette sub family E member 1 RNase L inhibitor Ribonuclease 4 inhibitor RNS4I 2 5 oligoadenylate binding
protein HuHP68 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
ORM1-like protein 3 Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4
6 tetrakisphosphate 5 kinase Homo sapiens Human
Nucleolar protein 66 hsNO66 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Zinc finger BED domain containing protein 4 Homo sapiens
Human
Keratin-associated protein 21 2 Homo sapiens Human
12404
12404
12404
12404
12404
12404
12397
12229
12378
12429
12429
12396
12524
12322
12322
12322
12322
12322
12322
12322
12322
12376
12376
197
1
2
3
4
186
4.75
12388
187
4.72
188
4.64
189
190
4.58
4.50
191
192
4.46
4.42
193
4.38
194
4.30
195
4.28
196
4.21
197
4.21
198
4.20
199
4.12
200
4.10
201
202
4.09
4.07
203
4.05
204
4.01
205
4.01
Mucin-3B Intestinal mucin 3B Fragment Homo sapiens Human
G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Uncharacterized protein C21orf62 B37 Homo sapiens Human
Transcription factor MafG V maf musculoaponeurotic fibrosarcoma oncogene homolog G hMAF Homo sapiens Human
Ubiquitin carboxyl terminal hydrolase 16 EC 3 1 2 15 Ubiquitin thioesterase 16 Ubiquitin specific processing protease 16
Deubiquitinating enzyme 16 Ubiquitin processing protease
UBP M Homo sapiens Human
Px19-like protein 25 kDa protein of relevant evolutionary and
lymphoid interest PRELI Homo sapiens Human
Telomeric repeat binding factor 2 TTAGGG repeat binding factor
2 Telomeric DNA binding protein Homo sapiens Human
ATP-binding cassette sub family E member 1 RNase L inhibitor Ribonuclease 4 inhibitor RNS4I 2 5 oligoadenylate binding
protein HuHP68 Homo sapiens Human
ATP-binding cassette sub family E member 1 RNase L inhibitor Ribonuclease 4 inhibitor RNS4I 2 5 oligoadenylate binding
protein HuHP68 Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4
6 tetrakisphosphate 5 kinase Homo sapiens Human
Killer cell immunoglobulin like receptor 2DL2 precursor
MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43
p58 NK receptorHomo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
PR domain zinc finger protein 15 PR domain containing protein 15 Zinc finger protein 298 Homo sapiens Human
Chondroitin sulfate glucuronyltransferase EC 2 4 1 226 N
acetylgalactosaminyl proteoglycan 3 beta glucuronosyltransferase Chondroitin glucuronyltransferase II CSGlcA T Homo
sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
12438
12267
12267
12267
12267
12561
12713
12590
12496
12346
12327
12588
12436
12626
12593
12402
12415
12415
12500
198
1
2
3
4
206
4.01
12352
207
3.99
208
3.98
209
3.93
210
3.93
211
3.92
212
3.91
213
3.88
214
215
3.81
3.78
216
217
3.73
3.70
218
3.70
219
220
3.68
3.67
221
3.64
222
3.64
223
3.64
224
3.63
225
3.62
226
3.59
227
3.55
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Ankyrin repeat domain containing protein 46 Ankyrin repeat
small protein ANK S Homo sapiens Human
Ankyrin repeat domain containing protein 46 Ankyrin repeat
small protein ANK S Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Long-chain-fatty-acid--CoA ligase 6 EC 6 2 1 3 Long chain
acyl CoA synthetase 6 LACS 6 Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
E3 ubiquitin protein ligase RNF19 EC 6 3 2 RING finger protein 19 Dorfin Double ring finger protein p38 protein Homo
sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Reticulon-2 Neuroendocrine specific protein like 1 NSP like
protein 1 NSPLI Homo sapiens Human
Reticulon-2 Neuroendocrine specific protein like 1 NSP like
protein 1 NSPLI Homo sapiens Human
Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Lysosomal-associated transmembrane protein 4A Golgi 4
transmembrane spanning transporter MTP Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Zinc finger BED domain containing protein 4 Homo sapiens
Human
Protein yippee like 4 Homo sapiens Human
12583
12307
12705
12274
12609
12383
12383
12377
12377
12377
12377
12377
12395
12585
12317
12372
12371
12277
12277
12277
12277
199
1
228
2
3.53
229
3.53
230
3.53
231
232
3.52
3.50
233
3.50
234
3.48
235
3.47
236
3.38
237
3.37
238
239
240
241
242
3.31
3.25
3.24
3.24
3.23
243
3.23
244
3.21
245
246
3.20
3.16
247
248
249
3.15
3.09
3.08
3
Probable phospholipid transporting ATPase IC EC 3 6 3 1
Familial intrahepatic cholestasis type 1 ATPase class I type 8B
member 1 Homo sapiens Human
Probable phospholipid transporting ATPase IC EC 3 6 3 1
Familial intrahepatic cholestasis type 1 ATPase class I type 8B
member 1 Homo sapiens Human
Probable phospholipid transporting ATPase IC EC 3 6 3 1
Familial intrahepatic cholestasis type 1 ATPase class I type 8B
member 1 Homo sapiens Human
MARVEL domain containing protein 1 Homo sapiens Human
ATP-binding cassette sub family E member 1 RNase L inhibitor Ribonuclease 4 inhibitor RNS4I 2 5 oligoadenylate binding
protein HuHP68 Homo sapiens Human
ATP-binding cassette sub family E member 1 RNase L inhibitor Ribonuclease 4 inhibitor RNS4I 2 5 oligoadenylate binding
protein HuHP68 Homo sapiens Human
BAX protein cytoplasmic isoform gamma Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Telomeric repeat binding factor 2 TTAGGG repeat binding factor
2 Telomeric DNA binding protein Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Uncharacterized protein C14orf128 Homo sapiens Human
Uncharacterized protein C14orf128 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Proteasome activator complex subunit 2 Proteasome activator
28 subunit beta PA28beta PA28b Activator of multicatalytic
protease subunit 2 11S regulator complex subunit beta REG
beta Homo sapiens Human
Sorting nexin 12 Homo sapiens Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Keratin-associated protein 21 2 Homo sapiens Human
Zinc finger protein 225 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
4
12277
12277
12277
12277
12277
12353
12614
12349
12452
12712
12591
12471
12399
12430
12314
12569
12407
12407
12467
12497
12497
12309
200
1
250
2
3.02
251
3.00
252
2.95
253
2.90
254
2.89
255
2.89
256
2.88
257
2.85
258
2.80
259
2.79
260
2.78
261
262
2.73
2.71
263
2.69
264
2.67
265
2.59
266
2.54
267
2.50
268
269
270
2.49
2.45
2.45
3
Uncharacterized protein C15orf41 Protein HH114 Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Selenocysteine-specific elongation factor Elongation factor sec
Eukaryotic elongation factor selenocysteine tRNA specific
Homo sapiens Human
Reticulon-2 Neuroendocrine specific protein like 1 NSP like
protein 1 NSPLI Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
B lymphocyte activation related protein BC 1514 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Myosin-Ia Brush border myosin I BBM I BBMI Myosin I
heavy chain MIHC Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Regulator of G protein signaling 18 RGS18 Homo sapiens
Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
POU domain class 2 associating factor 1 B cell specific coactivator OBF 1 OCT binding factor 1 BOB 1 OCA B Homo
sapiens Human
D(2 dopamine receptor Dopamine D2 receptor Homo sapiens
Human
Killer cell immunoglobulin like receptor 2DL2 precursor
MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43
p58 NK receptor Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Secretagogin Homo sapiens Human
Olfactomedin-like protein 1 precursor Homo sapiens Human
Olfactomedin-like protein 1 precursor Homo sapiens Human
4
12403
12403
12416
12416
12416
12505
12420
12408
12443
12443
12653
12310
12589
12392
12392
12398
12579
12498
12487
12522
12533
201
1
271
272
2
2.45
2.44
273
2.34
274
2.34
275
276
277
2.31
2.27
2.24
278
2.23
279
2.23
280
2.23
281
2.23
282
283
2.15
2.07
284
2.06
285
2.03
286
2.02
287
288
289
2.01
2.00
1.90
290
1.83
291
1.83
3
Olfactomedin-like protein 1 precursor Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
ER degradation enhancing alpha mannosidase like 1 Homo
sapiens Human
ER degradation enhancing alpha mannosidase like 1 Homo
sapiens Human
Protein FAM126B Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Regulator of nonsense transcripts 3A Nonsense mRNA reducing factor 3A Up frameshift suppressor 3 homolog A hUpf3
Homo sapiens Human
Regulator of nonsense transcripts 3A Nonsense mRNA reducing factor 3A Up frameshift suppressor 3 homolog A hUpf3
Homo sapiens Human
Regulator of nonsense transcripts 3A Nonsense mRNA reducing factor 3A Up frameshift suppressor 3 homolog A hUpf3
Homo sapiens Human
Regulator of nonsense transcripts 3A Nonsense mRNA reducing factor 3A Up frameshift suppressor 3 homolog A hUpf3
Homo sapiens Human
Olfactory receptor 51T1 Homo sapiens Human
Killer cell immunoglobulin like receptor 2DL2 precursor
MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43
p58 NK receptor Homo sapiens Human
Reticulon-2 Neuroendocrine specific protein like 1 NSP like
protein 1 NSPLI Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4
6 tetrakisphosphate 5 kinase Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Putative serum amyloid A 3 protein Homo sapiens Human
Reticulon-2 Neuroendocrine specific protein like 1 NSP like
protein 1 NSPLI Homo sapiens Human
Neudesin precursor Neuron derived neurotrophic factor Secreted protein of unknown function SPUF protein Homo sapiens Human
Neudesin precursor Neuron derived neurotrophic factor Secreted protein of unknown function SPUF protein Homo sapiens Human
4
12320
12384
12582
12615
12615
12362
12367
12367
12367
12367
12367
12367
12288
12518
12620
12198
12256
12256
12256
12256
12256
202
1
292
2
1.78
293
1.76
294
1.71
295
1.61
296
1.57
297
1.56
298
1.56
299
1.55
300
1.54
301
1.52
302
303
1.51
1.50
304
1.48
305
306
1.42
1.38
307
308
1.29
1.19
309
1.19
310
1.15
311
1.11
312
1.11
313
1.08
3
Protein phosphatase Slingshot homolog 2 EC 3 1 3 48 EC 3 1
3 16 SSH 2L hSSH 2L Homo sapiens Human
Carboxypeptidase E precursor EC 3 4 17 10 CPE Carboxypeptidase H CPH Enkephalin convertase Prohormone processing
carboxypeptidase Homo sapiens Human
Aldose reductase EC 1 1 1 21 AR Aldehyde reductase Homo
sapiens Human
Px19-like protein 25 kDa protein of relevant evolutionary and
lymphoid interest PRELI Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4
6 tetrakisphosphate 5 kinase Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4
6 tetrakisphosphate 5 kinase Homo sapiens Human
UDP-N-acetylglucosamine transporter Golgi UDP GlcNAc
transporter Solute carrier family 35 member A3 Homo sapiens
Human
Developmental pluripotency associated protein 2 Pluripotent
embryonic stem cell related protein 1 Homo sapiens Human
Mucin-3B Intestinal mucin 3B Fragment Homo sapiens Human
Claudin-10 OSP like protein Homo sapiens Human
Reticulon-2 Neuroendocrine specific protein like 1 NSP like
protein 1 NSPLI Homo sapiens Human
Regulator of G protein signaling 20 RGS20 Regulator of Gz
selective protein signaling 1 Gz selective GTPase activating
protein G z GAP Homo sapiens Human
Sorting nexin 12 Homo sapiens Human
Killer cell immunoglobulin like receptor 2DL2 precursor
MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43
p58 NK receptor Homo sapiens Human
MARVEL domain containing protein 1 Homo sapiens Human
Zinc/RING finger protein 4 precursor RING finger protein 204
Homo sapiens Human
Zinc/RING finger protein 4 precursor RING finger protein 204
Homo sapiens Human
AN1-type zinc finger protein 5 Zinc finger A20 domain containing protein 2 Zinc finger protein 216 Homo sapiens Human
Putative RNA binding protein 16 RNA binding motif protein
16 Homo sapiens Human
Putative RNA binding protein 16 RNA binding motif protein
16 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
4
12256
12256
12256
12699
12566
12271
12271
12271
12413
12413
12413
12413
12413
12413
12413
12413
12413
12413
12308
12578
12358
12706
203
1
314
2
1.05
315
1.02
316
317
318
319
320
1.00
0.95
0.93
0.79
0.77
321
0.75
322
0.74
323
0.73
324
0.72
325
0.68
326
327
0.67
0.64
328
0.60
329
0.60
330
331
0.52
0.50
332
0.47
333
334
335
0.39
0.37
0.37
3
Tubulin polymerization promoting protein TPPP 25 kDa brain
specific protein p25 alpha p24 p25 Homo sapiens Human
Translocator protein Peripheral type benzodiazepine receptor
PBR PKBS Mitochondrial benzodiazepine receptor Homo
sapiens Human
Dynamin-1-like
Protein mago nashi homolog Homo sapiens Human
Secretagogin Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
Killer cell immunoglobulin like receptor 2DL2 precursor
MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43
p58 NK receptor Homo sapiens Human
Cathepsin L2 precursor EC 3 4 22 43 Cathepsin V Cathepsin
U Homo sapiens Human
Homeobox protein Nkx 2 8 Homeobox protein NK 2 homolog
H Homo sapiens Human
DNA topoisomerase 2 binding protein 1 DNA topoisomerase
II binding protein 1 DNA topoisomerase IIbeta binding protein
1 TopBP1 Homo sapiens Human
Zinc finger HIT domain containing protein 1 Cyclin G1 binding protein 1 Homo sapiens Human
Aldehyde dehydrogenase dimeric NADP preferring EC 1 2 1 5
ALDH class 3 ALDHIII Homo sapiens Human
Microtubule-associated
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
ER degradation enhancing alpha mannosidase like 1 Homo
sapiens Human
ER degradation enhancing alpha mannosidase like 1 Homo
sapiens Human
Oncostatin-M precursor OSM Homo sapiens Human
Aldose reductase EC 1 1 1 21 AR Aldehyde reductase Homo
sapiens Human
Josephin-1 Josephin domain containing 1 Homo sapiens Human
Transcription factor Sp4 SPR 1 Homo sapiens Human
Syntaphilin Homo sapiens Human
Syntaphilin Homo sapiens Human
4
12696
12284
12240
12573
12217
12217
12217
12217
12217
12217
12217
12217
12217
12217
12217
12217
12428
12428
12366
12366
12531
12604
204
Ɍɚɛɥɢɰɚ 5
ȼɟɪɨɹɬɧɨɫɬɶ
ʋ ɩ/ɩ ɫɨɜɩɚɞɟɧɢɹ
(%)
1
2
1
2
88.76
87.06
3
4
5
77.43
77.19
76.17
6
7
63.35
52.53
8
9
10
51.69
47.45
46.38
11
46.32
12
44.22
13
42.47
14
41.90
15
16
41.76
41.52
17
39.08
18
36.61
19
36.48
20
33.91
21
22
23
24
33.54
33.16
32.85
32.66
ID ɛɟɥɤɨɜ ɞɥɹ CD34+ȽɋɄ (3-ɹ ɮɪɚɤɰɢɹ, 1-ɹ ɩɨɜɬɨɪɧɨɫɬɶ)
ɇɨɦɟɪ
ɩɹɬɧɚ
3
4
Zinc finger protein 225 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Cryptochrome-1 Homo sapiens Human
Cryptochrome-1 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human
Beta-adrenergic receptor kinase 1 EC 2 7 11 15 Beta ARK 1 G
protein coupled receptor kinase 2 Homo sapiens Human
Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human
Cryptochrome-1 Homo sapiens Human
E3 ubiquitin protein ligase HECW2 EC 6 3 2 HECT C2 and
WW domain containing protein 2 NEDD4 like ubiquitin protein ligase 2 Homo sapiens Human
Kinesin-like motor protein C20orf23 Sorting nexin 23 Homo
sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Acyl-coenzyme A thioesterase 4 EC 3 1 2 2 Acyl CoA thioesterase 4 Peroxisomal acyl coenzyme A thioester hydrolase Ib
Peroxisomal long chain acyl coA thioesterase Ib PTE Ib PTE
2b Homo sapiens Human
Cryptochrome-1 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
DNA repair protein RAD50 EC 3 6 hRAD50 Homo sapiens
Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Regulator of G protein signaling 13 RGS13 Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Regulator of G protein signaling 13 RGS13 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
504
711
209
73
588
210
231
604
97
353
226
695
519
201
267
561
616
554
240
292
233
574
221
603
205
1
2
3
4
25
32.62
898
26
32.27
27
30.86
28
29
30.70
29.52
30
31
28.05
27.92
32
27.33
33
27.15
34
35
25.83
25.02
36
24.23
37
38
23.51
23.50
39
23.22
40
23.16
41
22.90
42
22.25
43
21.72
44
45
21.08
21.04
46
20.83
47
20.45
48
19.69
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Kinesin-like protein KIF3A Microtubule plus end directed
kinesin motor 3A Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Suppressor of cytokine signaling 6 SOCS 6 Suppressor of
cytokine signaling 4 SOCS 4 Cytokine inducible SH2 protein
4 CIS 4 Homo sapiens Human
Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human
Glial fibrillary acidic protein astrocyte GFAP Homo sapiens
Human
Kinesin-like protein KIF3A Microtubule plus end directed
kinesin motor 3A Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Cryptochrome-1 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Histone deacetylase 10 HD10Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Sterol regulatory element binding protein 1 SREBP1 Sterol
regulatory element binding transcription factor 1 Homo sapiens Human
Glial fibrillary acidic protein astrocyte GFAP Homo sapiens
Human
Caspase recruitment domain containing protein 14 CARD
containing MAGUK protein 2 Carma 2 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Zinc finger BED domain containing protein 4 Homo sapiens
Human
Protein phosphatase Slingshot homolog 2 EC 3 1 3 48 EC 3 1
3 16 SSH 2L hSSH 2L Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
185
552
683
590
512
593
175
639
136
553
946
243
558
909
491
520
366
377
309
576
393
669
535
206
1
2
3
4
49
19.47
698
50
51
18.67
18.41
52
53
18.33
18.15
54
17.45
55
16.76
56
16.60
57
58
16.52
16.13
59
16.06
60
61
16.05
15.67
62
63
15.48
15.43
64
65
66
67
15.38
15.23
15.13
14.75
68
69
14.62
14.57
70
14.32
71
14.23
72
14.18
DNA polymerase sigma EC 2 7 7 7 Topoisomerase related
function protein 4 1 TRF4 1 LAK 1 DNA polymerase kappa
Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Uncharacterized protein C6orf60 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20
Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Calcium-transporting ATPase type 2C member 1 EC 3 6 3 8
ATPase 2C1 ATP dependent Ca 2 pump PMR1 Homo sapiens
Human
Bcl-2-modifying factor Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Uncharacterized protein C18orf54 precursor Homo sapiens Human
Zinc finger protein 225 Homo sapiens Human
Putative tyrosine protein phosphatase TPTE EC 3 1 3 48
Transmembrane phosphatase with tensin homology Protein BJ
HCC 5 Homo sapiens Human
Uncharacterized protein C6orf10 Homo sapiens Human
Keratin, type I cytoskeletal 23 Cytokeratin 23 CK 23 Keratin
23 K23 Homo sapiens Human
Neuronal PAS domain containing protein 1 Neuronal PAS1
Member of PAS protein 5 Basic helix loop helix PAS protein
MOP5 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
403
469
134
375
829
888
508
923
594
186
710
589
567
700
860
707
544
600
184
170
261
235
675
207
1
2
3
4
73
14.09
704
74
14.08
75
76
77
13.99
13.96
13.66
78
79
13.24
13.16
80
13.16
81
13.13
82
83
13.06
12.89
84
12.80
85
12.73
86
12.71
87
12.60
88
12.47
89
12.44
90
12.39
91
92
11.91
11.85
93
94
95
11.80
11.74
11.73
Rho guanine nucleotide exchange factor 5 Guanine nucleotide
regulatory protein TIM Oncogene TIM p60 TIM Transforming
immortalized mammary oncogene Homo sapiens Human
Sterol regulatory element binding protein 1 SREBP 1 Sterol
regulatory element binding transcription factor 1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
SAPS domain family member 2 Homo sapiens Human
CAP-GLY domain containing linker protein 2 Cytoplasmic
linker protein 2 Cytoplasmic linker protein 115 CLIP 115
Williams Beuren syndrome chromosome region 4 protein
Homo sapiens Human
CAP-GLY domain containing linker protein 2 Cytoplasmic
linker protein 2 Cytoplasmic linker protein 115 CLIP 115
Williams Beuren syndrome chromosome region 4 protein
Homo sapiens Human
Fizzy-related protein homolog Fzr Cdh1 Hct1 homolog
hCDH1 CDC20 like protein 1 Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
DNA repair protein RAD50 EC 3 6 hRAD50 Homo sapiens
Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Probable phospholipid transporting ATPase IF EC 3 6 3 1
ATPase class I type 11B ATPase IR Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20
Homo sapiens Human
Rho guanine nucleotide exchange factor 5 Guanine nucleotide
regulatory protein TIM Oncogene TIM p60 TIM Transforming
immortalized mammary oncogene Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Uncharacterized protein C18orf54 precursor Homo sapiens Human
Ephrin type B receptor 6 precursor Tyrosine protein kinase
defective receptor EPH 6 HEP Homo sapiens Human
503
836
892
703
264
271
271
220
478
487
622
395
679
943
904
279
514
213
823
852
575
161
208
1
2
96
11.67
Keratin-associated protein 21 2 Homo sapiens Human
3
427
4
97
11.67
Keratin-associated protein 21 2 Homo sapiens Human
427
98
11.65
668
99
100
11.59
11.54
101
11.51
102
11.34
103
11.33
104
11.28
105
11.25
106
107
108
11.21
11.19
11.05
109
11.03
110
10.76
111
10.72
112
10.71
113
10.66
114
10.63
115
10.44
116
10.44
117
10.35
118
10.23
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Serine/threonine-protein
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Uncharacterized protein C18orf54 precursor Homo sapiens
Human
Protocadherin gamma A10 precursor PCDH gamma A10 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Zinc finger protein 143 SPH binding factor Homo sapiens
Human
Nucleolar protein 66 hsNO66 Homo sapiens Human
Advillin p92 Homo sapiens Human
Chondroitin sulfate glucuronyltransferase EC 2 4 1 226 N
acetylgalactosaminyl proteoglycan 3 beta glucuronosyltransferase Chondroitin glucuronyltransferase II CSGlcA T Homo
sapiens Human
E3 ubiquitin protein ligase RNF19 EC 6 3 2 RING finger protein 19 Dorfin Double ring finger protein p38 protein Homo
sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Zinc finger BED domain containing protein 4 Homo sapiens
Human
Low-density lipoprotein receptor related protein 8 precursor
Apolipoprotein E receptor 2 Homo sapiens Human
Putative ATP dependent RNA helicase DHX33 EC 3 6 1
DEAH box protein 33 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Zinc finger BED domain containing protein 4 Homo sapiens
Human
251
509
699
490
159
498
270
691
222
706
531
349
502
563
656
596
406
406
693
628
209
1
2
3
4
119
10.23
628
120
10.13
121
10.02
122
9.97
123
9.95
124
125
126
127
128
129
9.83
9.78
9.77
9.75
9.70
9.57
130
9.56
131
9.55
132
9.50
133
134
9.46
9.39
135
9.39
136
9.36
137
138
9.32
9.30
139
9.25
140
9.16
141
9.01
142
8.98
Zinc finger BED domain containing protein 4 Homo sapiens
Human
Probable G protein coupled receptor 158 precursor Homo
sapiens Human
G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Putative tyrosine protein phosphatase TPTE EC 3 1 3 48
Transmembrane phosphatase with tensin homology Protein BJ
HCC 5 Homo sapiens Human
Cryptochrome-1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Solute
Secretagogin Homo sapiens Human
Mitochondrial intermediate peptidase mitochondrial precursor
EC 3 4 24 59 MIP Homo sapiens Human
Replication factor C subunit 2 Replication factor C 40 kDa
subunit RF C 40 kDa subunit RFC40 Activator 1 40 kDa subunit A1 40 kDa subunit Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Rho guanine nucleotide exchange factor 5 Guanine nucleotide
regulatory protein TIM Oncogene TIM p60 TIM Transforming
immortalized mammary oncogene Homo sapiens Human
Uncharacterized protein C21orf62 B37 Homo sapiens Human
G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human
G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human
G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
191
585
621
591
110
853
861
361
320
564
219
486
290
472
614
614
259
556
437
369
664
118
385
210
1
2
3
4
143
8.76
139
144
145
146
8.73
8.67
8.62
147
148
8.59
8.54
149
150
151
152
8.53
8.50
8.50
8.45
153
154
155
8.44
8.44
8.41
156
157
8.31
8.22
158
8.21
159
8.21
160
8.20
161
8.15
162
8.14
163
8.14
164
8.09
165
166
8.05
8.04
167
8.02
168
169
7.97
7.92
Kinesin-like protein KIF3A Microtubule plus end directed
kinesin motor 3A Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Krueppel-like factor 15 Kidney enriched krueppel like factor
Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
D-2-hydroxyglutarate dehydrogenase mitochondrial precursor
EC 1 1 99 Homo sapiens Human
Uncharacterized protein C20orf29 Homo sapiens Human
Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human
Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Protein HFSE 1 Homo sapiens Human
Protein HFSE 1 Homo sapiens Human
Chondroitin sulfate glucuronyltransferase EC 2 4 1 226 N
acetylgalactosaminyl proteoglycan 3 beta glucuronosyltransferase Chondroitin glucuronyltransferase II CSGlcA T Homo
sapiens Human
Bifunctional
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens
Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens
Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Rho guanine nucleotide exchange factor 5 Guanine nucleotide
regulatory protein TIM Oncogene TIM p60 TIM Transforming
immortalized mammary oncogene Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Uncharacterized protein C21orf62 B37 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Zinc finger and BTB domain containing protein 41 Homo
sapiens Human
Collagen alpha 2 VI chain precursor Homo sapiens Human
Uncharacterized protein C18orf54 precursor Homo sapiens Human
855
844
79
827
262
583
351
351
673
181
181
464
418
697
245
245
470
595
605
605
953
410
598
886
241
592
211
1
2
3
4
170
171
172
7.78
7.76
7.75
837
477
613
173
7.70
174
175
176
7.65
7.62
7.61
177
178
7.58
7.56
179
180
7.45
7.44
181
7.38
182
7.35
183
7.34
184
7.34
185
186
187
7.27
7.21
7.15
188
7.15
189
7.00
190
6.99
191
6.97
192
193
194
195
196
6.91
6.90
6.90
6.86
6.82
197
6.81
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Uncharacterized protein C21orf62 B37 Homo sapiens Human
Uncharacterized protein C2orf21 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Putative tyrosine protein phosphatase TPTE EC 3 1 3 48
Transmembrane phosphatase with tensin homology Protein BJ
HCC 5 Homo sapiens Human
PHD finger protein 8 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20
Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Secretagogin Homo sapiens Human
Angiopoietin-1 precursor ANG 1 Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20
Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20
Homo sapiens Human
Zinc finger and SCAN domain containing protein 4 Zinc finger protein 494 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Dynamin-1-like
Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human
Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human
Phosducin-like protein 2 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4
6 tetrakisphosphate 5 kinase Homo sapiens Human
507
447
570
546
518
381
188
582
511
247
364
364
453
547
645
645
390
479
539
562
317
317
199
696
370
212
1
2
3
4
198
6.81
370
199
6.81
200
6.72
201
6.65
202
6.65
203
6.59
204
6.56
205
6.54
206
6.48
207
6.42
208
6.42
210
6.34
211
6.31
212
6.30
213
6.30
214
215
6.28
6.24
216
217
218
219
6.21
6.18
6.12
6.08
220
6.05
221
6.04
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4
6 tetrakisphosphate 5 kinase Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4
6 tetrakisphosphate 5 kinase Homo sapiens Human
Uncharacterized protein C18orf54 precursor Homo sapiens
Human
Steroidogenic acute regulatory protein mitochondrial precursor
StAR StARD1 Homo sapiens Human
Steroidogenic acute regulatory protein mitochondrial precursor
StAR StARD1 Homo sapiens Human
Putative uncharacterized protein C10orf130 Homo sapiens
Human
Transcription factor AP 2 alpha AP2 alpha Activating enhancer binding protein 2 alpha AP 2 transcription factor Activator
protein 2 AP 2 Homo sapiens Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Elongation factor G 1 mitochondrial precursor mEF G 1 Elongation factor G1 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Ubiquitin carboxyl terminal hydrolase 42 EC 3 1 2 15 Ubiquitin thioesterase 42 Ubiquitin specific processing protease 42
Deubiquitinating enzyme 42 Homo sapiens Human
Hepatocyte nuclear factor 3 beta HNF 3B Forkhead box protein A2 Homo sapiens Human
Mitochondrial intermediate peptidase mitochondrial precursor
EC 3 4 24 59 MIP Homo sapiens Human
Mitochondrial intermediate peptidase mitochondrial precursor
EC 3 4 24 59 MIP Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Low-density lipoprotein receptor related protein 8 precursor
Apolipoprotein E receptor 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Regulator of nonsense transcripts 3A Nonsense mRNA reducing factor 3A Up frameshift suppressor 3 homolog A hUpf3
Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
370
497
445
445
543
640
612
560
391
391
501
870
348
348
454
662
905
357
430
610
165
638
213
1
2
3
4
222
223
5.96
5.86
215
263
224
225
5.81
5.80
226
227
228
5.78
5.77
5.73
229
230
5.72
5.68
231
232
233
234
5.60
5.53
5.53
5.52
235
236
237
238
239
5.51
5.49
5.46
5.46
5.44
240
241
5.37
5.30
242
243
244
245
5.29
5.29
5.27
5.26
246
247
248
249
5.20
5.20
5.15
5.12
250
5.11
251
252
253
254
5.10
5.09
5.09
5.06
Keratin-associated protein 21 2 Homo sapiens Human
Spartin Trans activated by hepatitis C virus core protein 1
Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Secretagogin Homo sapiens Human
Nucleolar protein 66 hsNO66 Homo sapiens Human
G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Protein Wnt 8a precursor Wnt 8d Homo sapiens Human
Cryptochrome-1 Homo sapiens Human
Cryptochrome-1 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Uncharacterized protein C21orf62 B37 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Histone deacetylase 10 HD10 Homo sapiens Human
Sterol regulatory element binding protein 1 SREBP 1 Sterol
regulatory element binding transcription factor 1 Homo sapiens Human
Brain-specific angiogenesis inhibitor 1 precursor Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Calcium-transporting ATPase type 2C member 1 EC 3 6 3 8
ATPase 2C1 ATP dependent Ca 2 pump PMR1 Homo sapiens
Human
316
945
300
601
967
919
319
890
297
297
580
426
677
254
254
537
534
876
840
840
468
432
433
433
355
678
413
428
329
329
147
214
1
2
3
4
255
5.02
500
256
5.00
257
258
4.99
4.98
259
4.96
260
4.96
261
4.91
262
263
4.90
4.86
264
4.80
265
4.80
266
4.76
267
4.75
268
4.74
269
270
271
272
4.72
4.72
4.72
4.70
273
4.68
274
4.67
275
4.65
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
ORM1-like protein 3 Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
MARVEL domain containing protein 1 Homo sapiens Human
E3 ubiquitin protein ligase RNF19 EC 6 3 2 RING finger protein 19 Dorfin Double ring finger protein p38 protein Homo
sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Hematopoietic progenitor cell antigen CD34 precursor Homo
sapiens Human
Ubiquitin carboxyl terminal hydrolase 16 EC 3 1 2 15 Ubiquitin thioesterase 16 Ubiquitin specific processing protease 16
Deubiquitinating enzyme 16 Ubiquitin processing protease
UBP M Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Zinc finger BED domain containing protein 4 Homo sapiens
Human
Antigen peptide transporter 2 APT2 ATP binding cassette sub
family B member 3 Peptide transporter TAP2 Peptide transporter PSF2 Peptide supply factor 2 PSF 2 Peptide transporter
involved in antigen processing 2 Homo sapiens Human
Putative tyrosine protein phosphatase TPTE EC 3 1 3 48
Transmembrane phosphatase with tensin homology Protein BJ
HCC 5 Homo sapiens Human
cAMP-dependent protein kinase inhibitor alpha PKI alpha
cAMP dependent protein kinase inhibitor muscle brain isoform
Homo sapiens Human
688
373
525
280
280
834
380
274
597
597
538
914
629
289
289
289
636
572
928
153
215
1
2
3
4
276
4.65
153
277
4.63
278
4.61
279
4.60
280
4.60
281
4.58
282
4.54
283
284
4.52
4.50
285
286
287
288
4.49
4.48
4.48
4.46
289
4.44
290
291
4.43
4.41
292
4.41
293
4.41
294
295
4.35
4.34
296
297
298
4.33
4.33
4.32
299
4.32
cAMP-dependent protein kinase inhibitor alpha PKI alpha
cAMP dependent protein kinase inhibitor muscle brain isoform
Homo sapiens Human
Probable palmitoyltransferase ZDHHC4 EC 2 3 1 Zinc finger
DHHC domain containing protein 4 DHHC 4 Zinc finger protein 374 Homo sapiens Human
Telomeric repeat binding factor 2 TTAGGG repeat binding
factor 2 Telomeric DNA binding protein Homo sapiens Human
Reticulon-2 Neuroendocrine specific protein like 1 NSP like
protein 1 NSPLI Homo sapiens Human
Reticulon-2 Neuroendocrine specific protein like 1 NSP like
protein 1 NSPLI Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Probable phospholipid transporting ATPase IC EC 3 6 3 1
Familial intrahepatic cholestasis type 1 ATPase class I type 8B
member 1 Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
UPF0407 protein C2orf39 Homo sapiens Human
Uncharacterized protein C6orf10 Homo sapiens Human
Uncharacterized protein C6orf10 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Zinc finger and BTB domain containing protein 26 Zinc finger
protein 481 Zinc finger protein Bioref Homo sapiens Human
L-myc-1 proto oncogene protein Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
542
388
295
295
626
882
223
272
452
269
269
365
485
527
298
298
298
420
960
307
307
360
360
216
1
2
3
4
300
4.31
359
301
4.25
302
303
4.24
4.23
304
305
4.17
4.13
306
4.13
307
308
309
310
4.12
4.12
4.12
4.08
311
4.07
312
4.07
313
4.07
314
4.01
315
4.00
316
3.97
317
3.95
318
3.94
319
3.92
320
3.91
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
E3 ubiquitin protein ligase RNF19 EC 6 3 2 RING finger protein 19 Dorfin Double ring finger protein p38 protein Homo
sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Kinesin-like protein KIF3A Microtubule plus end directed
kinesin motor 3A Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20
Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20
Homo sapiens Human
Uncharacterized protein C12orf5 Homo sapiens Human
Uncharacterized protein C12orf5 Homo sapiens Human
Uncharacterized protein C12orf5 Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
DNA-directed RNA polymerase I 135 kDa polypeptide EC 2 7
7 6 RNA polymerase I subunit 2 RPA135 Homo sapiens Human
Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo
sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
338
523
244
897
278
278
180
180
180
386
441
441
441
644
505
833
657
847
924
459
217
1
2
3
4
321
3.90
313
322
3.88
323
3.82
324
3.81
325
3.80
326
3.79
327
328
329
330
3.77
3.76
3.76
3.73
331
3.71
332
3.66
333
3.65
334
335
3.63
3.61
336
3.61
337
338
3.60
3.59
339
340
341
3.55
3.54
3.53
Chondroitin sulfate glucuronyltransferase EC 2 4 1 226 N
acetylgalactosaminyl proteoglycan 3 beta glucuronosyltransferase Chondroitin glucuronyltransferase II CSGlcA T Homo
sapiens Human
Reticulon-2 Neuroendocrine specific protein like 1 NSP like
protein 1 NSPLI Homo sapiens Human
Kinesin-like protein KIF3A Microtubule plus end directed
kinesin motor 3A Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Calcium-transporting ATPase type 2C member 1 EC 3 6 3 8
ATPase 2C1 ATP dependent Ca 2 pump PMR1 Homo sapiens
Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
NEDD4-binding protein 3 N4BP3 Homo sapiens Human
Zinc finger protein 691 Homo sapiens Human
Zinc finger protein 691 Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Regulator of G protein signaling 22 RGS22 Homo sapiens
Human
Probable phospholipid transporting ATPase IF EC 3 6 3 1
ATPase class I type 11B ATPase IR Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human
Suppressor of cytokine signaling 6 SOCS 6 Suppressor of
cytokine signaling 4 SOCS 4 Cytokine inducible SH2 protein
4 CIS 4 Homo sapiens Human
545
917
451
200
631
276
462
462
510
483
207
494
889
824
824
399
488
457
398
378
218
1
2
3
4
342
3.53
378
343
3.52
344
3.51
345
3.46
346
3.45
347
3.45
348
349
3.44
3.40
350
3.39
351
3.38
352
3.36
353
3.35
354
3.33
355
3.30
356
3.30
357
3.28
358
3.26
359
3.26
360
3.25
Suppressor of cytokine signaling 6 SOCS 6 Suppressor of
cytokine signaling 4 SOCS 4 Cytokine inducible SH2 protein
4 CIS 4 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Hexokinase-3 EC 2 7 1 1 Hexokinase type III HK III Homo
sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Keratin-associated protein 21 2 Homo sapiens Human
ER degradation enhancing alpha mannosidase like 1 Homo
sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Zinc finger protein 143 SPH binding factor Homo sapiens
Human
Nuclear pore complex protein Nup98 Nup96 precursor Contains Nuclear pore complex protein Nup98 Nucleoporin Nup98
98 kDa nucleoporin Nuclear pore complex protein Nup96
Nucleoporin Nup96 96 kDa nucleoporin Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Probable phospholipid transporting ATPase ID EC 3 6 3 1
ATPase class I type 8B member 2 Homo sapiens Human
Probable phospholipid transporting ATPase ID EC 3 6 3 1
ATPase class I type 8B member 2 Homo sapiens Human
DNA topoisomerase 2 binding protein 1 DNA topoisomerase
II binding protein 1 DNA topoisomerase IIbeta binding protein
1 TopBP1 Homo sapiens Human
PH domain leucine rich repeat protein phosphatase like EC 3 1
3 16 Homo sapiens Human
PH domain leucine rich repeat protein phosphatase like EC 3 1
3 16 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
828
651
825
526
526
440
599
619
256
333
205
637
202
202
513
284
284
666
219
1
2
3
4
361
3.25
666
362
363
3.23
3.19
364
3.16
365
3.16
366
3.15
367
3.15
368
3.14
369
3.10
370
3.10
371
3.08
372
3.08
373
3.06
374
3.06
375
3.03
376
377
378
3.02
3.02
3.01
379
2.99
380
381
382
2.98
2.98
2.98
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Zinc finger protein 225 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
COUP transcription factor 2 COUP TF2 COUP TF II Apolipoprotein AI regulatory protein 1 ARP 1 Homo sapiens Human
COUP transcription factor 2 COUP TF2 COUP TF II Apolipoprotein AI regulatory protein 1 ARP 1 Homo sapiens Human
Beta-mannosidase precursor EC 3 2 1 25 Lysosomal beta A
mannosidase Mannanase Mannase Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
SH3 protein expressed in lymphocytes homolog Homo sapiens
Human
Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human
Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
236
489
356
356
182
182
940
649
649
414
414
392
392
408
285
285
415
475
436
436
436
220
1
2
383
2.98
Keratin-associated protein 21 2 Homo sapiens Human
3
436
4
384
2.94
694
385
2.88
386
2.88
387
2.87
388
2.86
389
2.86
390
2.86
391
392
2.85
2.84
393
2.83
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human
LIM domain transcription factor LMO4 LIM domain only
protein 4 LMO 4 Breast tumor autoantigen Homo sapiens
Human
LIM domain transcription factor LMO4 LIM domain only
protein 4 LMO 4 Breast tumor autoantigen Homo sapiens
Human
LIM domain transcription factor LMO4 LIM domain only
protein 4 LMO 4 Breast tumor autoantigen Homo sapiens
Human
Profilin-3 Profilin III Homo sapiens Human
Late cornified envelope protein 3C Late envelope protein 15
Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human
Zinc finger protein 560 Homo sapiens Human
394
2.83
Zinc finger protein 560 Homo sapiens Human
466
395
2.82
402
396
2.82
397
2.81
398
2.77
399
2.76
400
2.76
401
2.75
402
2.75
403
2.74
Treacle protein Treacher Collins syndrome protein Homo
sapiens Human
Treacle protein Treacher Collins syndrome protein Homo
sapiens Human
Cullin-associated NEDD8 dissociated protein 2 Cullin associated and neddylation dissociated protein 2 p120 CAND2
Homo sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Methionyl-tRNA synthetase cytoplasmic EC 6 1 1 10 Methionine tRNA ligase MetRS Homo sapiens Human
Methionyl-tRNA synthetase cytoplasmic EC 6 1 1 10 Methionine tRNA ligase MetRS Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
273
273
571
132
132
132
315
891
466
402
586
559
211
211
660
660
294
221
1
2
3
4
404
2.73
826
405
2.71
406
2.70
407
2.69
408
2.69
409
2.68
410
2.68
411
2.67
412
2.66
413
2.63
414
2.63
415
2.62
416
2.62
417
2.62
418
2.61
419
2.60
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Hemoglobin subunit gamma 1 Hemoglobin gamma 1 chain
Gamma 1 globin Hemoglobin gamma A chain Hb F Agamma
Homo sapiens Human
G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human
Chondroitin sulfate glucuronyltransferase EC 2 4 1 226 N
acetylgalactosaminyl proteoglycan 3 beta glucuronosyltransferase Chondroitin glucuronyltransferase II CSGlcA T Homo
sapiens Human
Chondroitin sulfate glucuronyltransferase EC 2 4 1 226 N
acetylgalactosaminyl proteoglycan 3 beta glucuronosyltransferase Chondroitin glucuronyltransferase II CSGlcA T Homo
sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Interleukin-18 receptor 1 precursor IL1 receptor related protein
IL 1Rrp CD218a antigen CDw218a Homo sapiens Human
Interleukin-18 receptor 1 precursor IL1 receptor related protein
IL 1Rrp CD218a antigen CDw218a Homo sapiens Human
Interleukin-18 receptor 1 precursor IL1 receptor related protein
IL 1Rrp CD218a antigen CDw218a Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
208
961
383
383
609
609
653
281
634
634
178
178
178
529
654
222
1
2
3
4
420
2.60
654
421
2.59
422
2.59
423
2.58
424
2.55
425
2.54
426
2.53
427
2.52
428
2.52
429
2.52
430
2.51
431
2.51
432
433
434
435
436
437
2.50
2.49
2.48
2.47
2.47
2.46
438
2.46
439
2.45
440
2.43
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG like
protein Gastrointestinal secretory protein Homo sapiens Human
Tubulin-specific chaperone cofactor E like protein EL Leucine
rich repeat containing protein 35 Homo sapiens Human
Heat-shock protein beta 3 HspB3 Heat shock 17 kDa protein
Homo sapiens Human
Zinc finger MYM type protein 3 Zinc finger protein 261 Homo
sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Late cornified envelope protein 3C Late envelope protein 15
Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human
Late cornified envelope protein 3C Late envelope protein 15
Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
Collagen alpha 1 XVI chain precursor Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human
Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Zinc finger protein 250 Zinc finger protein 647 Homo sapiens
Human
555
555
407
193
968
857
471
471
471
620
620
277
431
894
423
423
305
305
350
382
223
1
2
3
4
441
442
2.42
2.40
618
367
443
2.40
444
445
446
447
2.37
2.34
2.31
2.30
448
2.30
449
2.29
Transmembrane protein 106B Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Syntaphilin Homo sapiens Human
Calpain-5 EC 3 4 22 nCL 3 htra 3 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Neuropeptide B precursor Preproprotein L7 hPPL7 Contains
Neuropeptide B 23 NPB23 hL7 Neuropeptide B 29 NPB29
hL7C Homo sapiens Human
Neuropeptide B precursor Preproprotein L7 hPPL7 Contains
Neuropeptide B 23 NPB23 hL7 Neuropeptide B 29 NPB29
hL7C Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
450
2.27
451
367
670
242
463
384
384
311
633
2.23
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human
452
2.22
Keratin-associated protein 21 2 Homo sapiens Human
435
453
2.19
303
454
2.19
455
2.16
456
2.15
457
2.12
458
2.11
459
2.11
460
2.11
461
2.10
462
2.10
463
2.08
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
ER degradation enhancing alpha mannosidase like 1 Homo
sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
PHD finger protein 21A BRAF35 HDAC complex protein
BHC80 BHC80a Homo sapiens Human
PHD finger protein 21A BRAF35 HDAC complex protein
BHC80 BHC80a Homo sapiens Human
PHD finger protein 21A BRAF35 HDAC complex protein
BHC80 BHC80a Homo sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
926
303
275
372
296
325
325
325
409
409
299
224
1
2
464
2.08
465
2.08
466
467
2.06
2.05
468
2.02
469
2.01
470
471
2.00
1.98
472
1.96
473
1.95
474
1.94
3
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
BAX protein cytoplasmic isoform gamma Homo sapiens Human
Glutaryl-CoA dehydrogenase mitochondrial precursor EC 1 3
99 7 GCD Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Serine/threonine-protein kinase Pim 3 EC 2 7 11 1 Homo sapiens Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Uncharacterized protein C18orf54 precursor Homo sapiens
Human
Keratin-associated protein 21 2 Homo sapiens Human
4
299
299
446
324
550
971
421
659
460
687
190
475
1.94
Keratin-associated protein 21 2 Homo sapiens Human
190
476
1.93
839
477
1.92
478
1.92
479
1.91
Adenylate cyclase type 9 EC 4 6 1 1 Adenylate cyclase type
IX ATP pyrophosphate lyase 9 Adenylyl cyclase 9 Homo
sapiens Human
Glutaryl-CoA dehydrogenase mitochondrial precursor EC 1 3
99 7 GCD Homo sapiens Human
Glutaryl-CoA dehydrogenase mitochondrial precursor EC 1 3
99 7 GCD Homo sapiens Human
Melanocortin receptor 5 MC5 R MC 2 Homo sapiens Human
480
1.91
Melanocortin receptor 5 MC5 R MC 2 Homo sapiens Human
214
481
1.89
Transmembrane protein 106B Homo sapiens Human
533
482
1.88
540
483
484
485
1.87
1.87
1.84
486
1.82
Integrin-linked protein kinase EC 2 7 11 1 ILK 1 ILK 2 59
kDa serine threonine protein kinase p59ILK Homo sapiens
Human
Protein yippee like 4 Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
419
487
1.82
Keratin-associated protein 21 2 Homo sapiens Human
419
488
1.82
Keratin-associated protein 21 2 Homo sapiens Human
419
354
354
214
293
293
663
225
1
2
489
1.81
3
4
Regulator of differentiation 1 Rod1 Homo sapiens Human
258
400
490
1.80
PHD finger protein 8 Homo sapiens Human
491
1.79
Transmembrane protein 106B Homo sapiens Human
346
492
1.76
Cadherin-like protein 26 precursor Cadherin like protein VR20
Homo sapiens Human
260
493
1.75
671
494
1.74
495
1.73
496
1.72
497
1.72
498
1.72
499
1.68
Reticulon-2 Neuroendocrine specific protein like 1 NSP like
protein 1 NSPLI Homo sapiens Human
MAM domain containing protein 2 precursor Homo sapiens
Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Calcium-transporting ATPase type 2C member 1 EC 3 6 3 8
ATPase 2C1 ATP dependent Ca 2 pump PMR1 Homo sapiens
Human
Calcium-transporting ATPase type 2C member 1 EC 3 6 3 8
ATPase 2C1 ATP dependent Ca 2 pump PMR1 Homo sapiens
Human
Calcium-transporting ATPase type 2C member 1 EC 3 6 3 8
ATPase 2C1 ATP dependent Ca 2 pump PMR1 Homo sapiens
Human
Peroxisome
500
1.67
501
1.67
502
1.64
503
1.62
504
1.62
505
1.60
506
1.58
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Regulator of G protein signaling 22 RGS22 Homo sapiens
Human
Regulator of G protein signaling 22 RGS22 Homo sapiens
Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4
6 tetrakisphosphate 5 kinase Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
507
1.58
Transmembrane protein 106B Homo sapiens Human
508
1.58
Transmembrane protein 106B Homo sapiens Human
143
509
1.56
Cullin-4B CUL 4B Homo sapiens Human
458
854
900
158
158
158
376
283
283
541
248
248
310
143
143
510
1.56
Cullin-4B CUL 4B Homo sapiens Human
458
511
1.54
Ankyrin repeat family A protein 2 RFXANK like 2 Homo
sapiens Human
166
226
1
2
3
4
512
1.52
116
513
1.52
514
1.49
515
1.44
516
1.41
517
1.40
518
1.40
519
1.40
520
1.39
521
1.38
522
1.38
523
1.37
524
1.35
525
526
1.31
1.30
527
1.29
528
1.28
529
1.28
E3 ubiquitin protein ligase MIB2 EC 6 3 2 Mind bomb homolog 2 Zinc finger ZZ type with ankyrin repeat domain protein 1
Skeletrophin Novelzin Novel zinc finger protein Putative NF
kappa B activating protein 002N Homo sapiens Human
E3 ubiquitin protein ligase MIB2 EC 6 3 2 Mind bomb homolog 2 Zinc finger ZZ type with ankyrin repeat domain protein 1
Skeletrophin Novelzin Novel zinc finger protein Putative NF
kappa B activating protein 002N Homo sapiens Human
Coiled-coil domain containing protein 85A Homo sapiens
Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Ubiquitin carboxyl terminal hydrolase 13 EC 3 1 2 15 Ubiquitin thioesterase 13 Ubiquitin specific processing protease 13
Deubiquitinating enzyme 13 Isopeptidase T 3 ISOT 3 Homo
sapiens Human
Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo
sapiens Human
Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo
sapiens Human
Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo
sapiens Human
Zinc finger protein 295 Zinc finger and BTB domain containing protein 21 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Alpha-(1,3)-fucosyltransferase EC 2 4 1 Galactoside 3 L fucosyltransferase Fucosyltransferase 9 FucT IX Homo sapiens
Human
Complex I intermediate associated protein 30 mitochondrial
precursorNADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Sorting nexin 22 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Hemoglobin subunit gamma 1 Hemoglobin gamma 1 chain
Gamma 1 globin Hemoglobin gamma A chain Hb F Agamma
Homo sapiens Human
Toll-interleukin 1 receptor domain containing adapter protein
TIR domain containing adapter protein MyD88 adapter like
protein Adaptor protein Wyatt Homo sapiens Human
Toll-interleukin 1 receptor domain containing adapter protein
TIR domain containing adapter protein MyD88 adapter like
protein Adaptor protein Wyatt Homo sapiens Human
116
617
843
443
239
239
239
492
140
140
198
321
169
162
196
515
515
227
1
2
3
4
530
531
1.24
1.23
872
314
532
1.21
533
1.20
534
535
1.18
1.17
536
1.15
537
538
1.12
0.97
539
540
0.95
0.94
541
542
0.93
0.89
543
0.89
544
545
0.87
0.85
546
0.85
547
0.84
Ubiquitin Homo sapiens Human
Steroidogenic acute regulatory protein mitochondrial precursor
StAR StARD1 Homo sapiens Human
Zinc finger protein ZIC 1 Zinc finger protein of the cerebellum
1 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Uncharacterized protein C8orf46 Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Keratin, type I cytoskeletal 9 Cytokeratin 9 CK 9 Keratin 9 K9
Homo sapiens Human
Protein mago nashi homolog Homo sapiens Human
Late cornified envelope protein 3C Late envelope protein 15
Small proline rich like epidermal differentiation complex protein 3A Homo sapiens Human
UPF0193 protein EVG1 Homo sapiens Human
ER degradation enhancing alpha mannosidase like 1 Homo
sapiens Human
Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human
Putative potassium channel regulatory protein Potassium
channel regulator Protein CLLD4 Homo sapiens Human
Putative potassium channel regulatory protein Potassium
channel regulator Protein CLLD4 Homo sapiens Human
Thrombospondin-3 precursor Homo sapiens Human
Melanotransferrin precursor Melanoma associated antigen p97
CD228 antigen Homo sapiens Human
Melanotransferrin precursor Melanoma associated antigen p97
CD228 antigen Homo sapiens Human
Cathepsin E precursor EC 3 4 23 34 Homo sapiens Human
194
548
0.77
Uncharacterized protein C21orf59 Homo sapiens Human
429
549
0.73
389
550
551
0.70
0.66
552
0.65
553
0.65
554
555
0.63
0.57
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4
6 tetrakisphosphate 5 kinase Homo sapiens Human
Protein FAM101B Homo sapiens Human
Williams-Beuren syndrome chromosome region 23 protein
Homo sapiens Human
Orphan nuclear receptor EAR 2 V erbA related protein EAR 2
Homo sapiens Human
Orphan nuclear receptor EAR 2 V erbA related protein EAR 2
Homo sapiens Human
Sodium-dependent
E3 ubiquitin protein ligase RING1 EC 6 3 2 Polycomb complex protein RING1 RING finger protein 1 Homo sapiens
Human
234
416
257
334
412
405
227
216
578
607
183
183
126
232
232
291
302
149
149
179
450
228
1
2
3
4
556
0.55
217
557
0.55
558
0.51
559
560
0.48
0.45
561
0.42
562
0.36
cAMP-dependent protein kinase inhibitor alpha PKI alpha
cAMP dependent protein kinase inhibitor muscle brain isoform
Homo sapiens Human
cAMP-dependent protein kinase inhibitor alpha PKI alpha
cAMP dependent protein kinase inhibitor muscle brain isoform
Homo sapiens Human
G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human
Homeobox protein GSH 1 Homo sapiens Human
Acyl-coenzyme A thioesterase 12 EC 3 1 2 1 Acyl CoA
thioesterase 12 Acyl CoA thioester hydrolase 12 Cytoplasmic
acetyl CoA hydrolase 1 CACH 1 hCACH 1 START domain
containing protein 12 StARD12 Homo sapiens Human
Small nuclear ribonucleoprotein Sm D2 snRNP core protein
D2 Sm D2 Homo sapiens Human
Embryonic growth differentiation factor 1 precursor GDF 1
Homo sapiens Human
217
625
871
225
506
681
229
Ɍɚɛɥɢɰɚ 6
ȼɟɪɨɹɬɧɨɫɬɶ
ʋ ɩ/ɩ ɫɨɜɩɚɞɟɧɢɹ
(%)
1
2
1
90.17
2
87.80
3
45.58
4
44.70
5
43.18
6
42.89
7
8
42.31
41.41
9
39.39
10
11
38.24
35.17
12
34.91
13
31.55
14
30.40
15
29.82
16
17
29.21
26.86
18
26.73
19
26.53
20
25.88
ID ɛɟɥɤɨɜ ɞɥɹ CD34+ȽɋɄ (3-ɹ ɮɪɚɤɰɢɹ, 2-ɹ ɩɨɜɬɨɪɧɨɫɬɶ)
ɇɨɦɟɪ
ɩɹɬɧɚ
3
4
Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1
CD316 antigen Homo sapiens Human
Selenocysteine-specific elongation factor Elongation factor sec
Eukaryotic elongation factor selenocysteine tRNA specific
Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Lamin-B2 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Killer cell immunoglobulin like receptor 2DL2 precursor
MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43
p58 NK receptor Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
12902
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
12805
13205
12815
13101
13197
12990
12914
12811
12901
12933
12889
12946
12924
12923
13014
12844
13066
12831
12836
230
1
2
3
4
21
25.65
13060
22
23.22
23
23.03
24
25
22.71
22.61
26
22.38
27
22.21
28
21.73
29
21.60
30
21.36
31
20.81
32
20.60
33
20.56
34
20.53
35
20.31
36
20.16
37
20.07
38
19.55
39
19.40
40
19.36
41
18.21
42
18.18
43
18.00
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Glycerol-3-phosphate acyltransferase mitochondrial precursor
EC 2 3 1 15 GPAT Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
E3 ubiquitin protein ligase RNF19 EC 6 3 2 RING finger protein 19 Dorfin Double ring finger protein p38 protein Homo
sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20
Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Zinc finger BED domain containing protein 4 Homo sapiens
Human
Rho guanine nucleotide exchange factor 5 Guanine nucleotide
regulatory protein TIM Oncogene TIM p60 TIM Transforming
immortalized mammary oncogene Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Zinc finger BED domain containing protein 4 Homo sapiens
Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Neuromedin-U receptor 1 NMU R1 G protein coupled receptor 66 G protein coupled receptor FM 3 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
12860
12912
13057
12911
12814
13166
12798
13167
12855
13056
12791
12870
12909
12837
12858
13200
13078
12884
12908
12929
12925
12896
231
1
2
3
4
44
16.83
13196
45
16.29
46
47
15.87
15.81
48
49
50
15.79
14.93
14.83
51
14.60
52
53
14.55
14.17
54
13.86
55
13.72
56
13.65
57
13.18
58
12.78
59
12.51
60
12.41
61
12.35
62
12.21
63
64
12.04
11.60
65
11.19
66
67
10.95
10.85
68
10.59
69
10.58
Uncharacterized protein C18orf54 precursor Homo sapiens
Human
PH domain leucine rich repeat protein phosphatase like EC 3 1
3 16 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Myosin-Ia Brush border myosin I BBM I BBMI Myosin I
heavy chain MIHC Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore glycoprotein p62 62 kDa nucleoporin Homo
sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4
6 tetrakisphosphate 5 kinase Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Putative tyrosine protein phosphatase TPTE EC 3 1 3 48
Transmembrane phosphatase with tensin homology Protein BJ
HCC 5 Homo sapiens Human
Protein transport protein Sec24D SEC24 related protein D
Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
12872
12957
12907
13106
12978
12838
12894
12988
13117
12968
12900
13173
13054
12921
13131
12890
13116
12932
13041
13063
12879
12951
12934
13027
12945
232
1
2
3
4
70
10.52
13065
71
72
10.48
10.39
73
10.38
74
10.07
75
9.97
76
9.83
77
9.55
78
79
80
9.43
9.38
9.15
81
9.07
82
9.03
83
84
8.69
8.60
85
86
8.46
8.37
87
88
8.34
8.31
89
8.30
90
8.15
91
8.01
92
8.01
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Solute carrier family 2 facilitated glucose transporter member
10 Glucose transporter type 10 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Uncharacterized protein C18orf54 precursor Homo sapiens
Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Putative tyrosine protein phosphatase TPTE EC 3 1 3 48
Transmembrane phosphatase with tensin homology Protein BJ
HCC 5 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Keratin-associated protein 21 2 Homo sapiens Human
Zinc finger and BTB domain containing protein 41 Homo
sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Anaphase-promoting complex subunit 4 APC4 Cyclosome
subunit 4 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Probable phospholipid transporting ATPase IF EC 3 6 3 1
ATPase class I type 11B ATPase IR Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Putative tyrosine protein phosphatase TPTE EC 3 1 3 48
Transmembrane phosphatase with tensin homology Protein BJ
HCC 5 Homo sapiens Human
Putative tyrosine protein phosphatase TPTE EC 3 1 3 48
Transmembrane phosphatase with tensin homology Protein BJ
HCC 5 Homo sapiens Human
12998
12835
13127
12972
13030
12887
13204
13073
13070
12859
13047
13023
12970
12996
12981
13034
12984
13142
12953
12874
12808
12808
233
1
2
3
4
93
7.92
13141
94
7.87
95
7.78
96
7.58
97
98
7.53
7.46
99
7.31
100
7.29
101
102
7.27
7.17
103
7.02
104
7.00
105
6.95
Selenocysteine-specific elongation factor Elongation factor sec
Eukaryotic elongation factor selenocysteine tRNA specific
Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Chondroitin sulfate glucuronyltransferase EC 2 4 1 226 N
acetylgalactosaminyl proteoglycan 3 beta glucuronosyltransferase Chondroitin glucuronyltransferase II CSGlcA T Homo
sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Protein BEX1 Brain expressed X linked protein 1 Homo sapiens Human
Putative tyrosine protein phosphatase TPTE EC 3 1 3 48
Transmembrane phosphatase with tensin homology Protein BJ
HCC 5 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human
Rho guanine nucleotide exchange factor 5 Guanine nucleotide
regulatory protein TIM Oncogene TIM p60 TIM Transforming
immortalized mammary oncogene Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
106
6.89
Keratin-associated protein 21 2 Homo sapiens Human
107
6.88
108
6.86
HMG box containing protein 1 HMG box transcription factor 13121
1 High mobility group box transcription factor 1 Homo sapiens
Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
12904
153 kDa nucleoporin Homo sapiens Human
109
6.85
110
6.67
111
6.67
112
6.66
13090
12862
13084
12987
13076
13111
13048
12969
13119
12821
13124
12982
12960
Actin-binding Rho activating protein Striated muscle activator 13104
of Rho dependent signaling STARS Homo sapiens Human
Selenocysteine-specific elongation factor Elongation factor sec 12916
Eukaryotic elongation factor selenocysteine tRNA specific
Homo sapiens Human
Selenocysteine-specific elongation factor Elongation factor sec 12916
Eukaryotic elongation factor selenocysteine tRNA specific
Homo sapiens Human
Sterol regulatory element binding protein 1 SREBP 1 Sterol
13197
regulatory element binding transcription factor 1 Homo sapiens Human
234
1
2
3
4
113
6.65
12952
114
6.65
115
116
117
118
119
120
121
6.54
6.51
6.49
6.48
6.48
6.46
6.37
122
6.33
123
6.32
124
6.21
125
6.21
126
6.16
127
6.13
128
6.11
129
6.10
130
6.05
131
6.04
132
6.01
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
L-myc-1 proto oncogene protein Homo sapiens Human
Uncharacterized protein C2orf21 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20
Homo sapiens Human
Protein BEX1 Brain expressed X linked protein 1 Homo sapiens Human
Pantothenate kinase 3 EC 2 7 1 33 Pantothenic acid kinase 3
hPanK3 Homo sapiens Human
Pantothenate kinase 3 EC 2 7 1 33 Pantothenic acid kinase 3
hPanK3 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Glial fibrillary acidic protein astrocyte GFAP Homo sapiens
Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4
6 tetrakisphosphate 5 kinase Homo sapiens Human
G-protein-signaling modulator 1 Activator of G protein signaling 3 Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
133
5.92
Transmembrane protein 106B Homo sapiens Human
12962
134
5.91
13172
135
5.84
136
5.83
137
5.76
Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1
CD316 antigen Homo sapiens Human
Putative tyrosine protein phosphatase TPTE EC 3 1 3 48
Transmembrane phosphatase with tensin homology Protein BJ
HCC 5 Homo sapiens Human
Prostaglandin D2 receptor Prostanoid DP receptor PGD receptor Homo sapiens Human
Uncharacterized protein C2orf21 Homo sapiens Human
12952
13087
13151
12839
12989
12989
13039
13082
12883
13162
12986
12986
13170
12829
12863
12944
12849
12828
12955
13208
12977
12927
235
1
2
3
4
138
5.74
13126
139
140
5.66
5.58
141
142
5.52
5.46
143
144
145
5.43
5.40
5.38
146
5.32
147
5.31
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
40S ribosomal protein S12 Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Keratin-associated protein 21 2 Homo sapiens Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Uncharacterized protein C2orf21 Homo sapiens Human
Band 4 1 like protein 4A Protein NBL4 Homo sapiens Human
Immunoglobulin superfamily member 8 precursor CD81 partner 3 Glu Trp Ile EWI motif containing protein 2 EWI 2 Keratinocytes associated transmembrane protein 4 KCT 4 LIR D1
CD316 antigen Homo sapiens Human
Arginine-glutamic acid dipeptide repeats protein Atrophin 1
like protein Atrophin 1 related protein Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
148
5.31
Keratin-associated protein 21 2 Homo sapiens Human
13013
149
5.28
13136
150
151
5.26
5.24
152
5.23
153
4.93
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Transcription factor AP 2 alpha AP2 alpha Activating enhancer binding protein 2 alpha AP 2 transcription factor Activator
protein 2 AP 2 Homo sapiens Human
Collagen alpha 1 XVI chain precursor Homo sapiens Human
13025
154
4.93
Collagen alpha 1 XVI chain precursor Homo sapiens Human
13025
155
4.89
12920
156
157
4.88
4.83
158
4.81
159
4.70
160
161
4.65
4.59
162
4.58
163
4.46
Phosphofurin acidic cluster sorting protein 2 PACS 2 PACS1
like protein Homo sapiens Human
Transmembrane protein 106BHomo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Methionyl-tRNA synthetase cytoplasmic EC 6 1 1 10 Methionine tRNA ligase MetRS Homo sapiens Human
Gamma crystallin C Gamma crystallin 2 1 Gamma crystallin 3
Homo sapiens Human
Frizzled-7 precursor Fz 7 hFz7 FzE3 Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4
6 tetrakisphosphate 5 kinase Homo sapiens Human
Low-density lipoprotein receptor related protein 8 precursor
Apolipoprotein E receptor 2 Homo sapiens Human
Bcl-2-modifying factor Homo sapiens Human
13175
12958
12975
12868
12818
12880
13046
13043
13013
12995
12922
13209
12959
12938
13091
12878
12948
12903
13105
13040
236
1
2
3
4
164
4.44
13138
165
4.41
166
4.41
167
4.40
168
4.33
169
170
171
4.30
4.22
4.20
172
4.18
173
4.17
174
4.16
175
4.16
176
4.11
177
4.07
178
179
180
181
4.04
4.04
4.02
3.98
182
3.98
183
184
185
3.92
3.88
3.78
186
3.78
PCI domain containing protein 2 CSN12 like protein Homo
sapiens Human
Transcription factor AP 2 alpha AP2 alpha Activating enhancer binding protein 2 alpha AP 2 transcription factor Activator
protein 2 AP 2 Homo sapiens Human
Transcription factor AP 2 alpha AP2 alpha Activating enhancer binding protein 2 alpha AP 2 transcription factor Activator
protein 2 AP 2 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Retinol dehydrogenase 12 EC 1 1 1 All trans and 9 cis retinol
dehydrogenase Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Uncharacterized protein C2orf14 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Probable G protein coupled receptor 61 Biogenic amine receptor like G protein coupled receptor Homo sapiens Human
Putative ATP dependent RNA helicase DHX33 EC 3 6 1
DEAH box protein 33 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Thromboxane A2 receptor TXA2 R Prostanoid TP receptor
Homo sapiens Human
Uncharacterized protein C2orf21 Homo sapiens Human
Uncharacterized protein C2orf21 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Transmembrane protein 106B Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Uncharacterized protein C18orf54 precursor Homo sapiens
Human
Uncharacterized protein C18orf54 precursor Homo sapiens
Human
12926
12926
13067
13109
13004
13154
13016
13168
12891
12832
12832
12939
13201
13031
13031
12999
12966
12966
13026
13005
12803
12803
237
1
2
3
4
187
3.76
12840
188
3.71
189
3.65
190
3.63
191
3.56
192
3.53
193
3.51
194
195
196
197
198
3.47
3.42
3.33
3.31
3.28
199
3.28
200
3.25
201
3.23
202
3.22
203
3.18
204
3.17
205
206
3.16
3.15
207
3.12
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
B lymphocyte activation related protein BC 1514 Homo sapiens Human
Cytochrome P450 4F8 EC 1 14 14 1 CYPIVF8 Homo sapiens
Human
Reticulon-2 Neuroendocrine specific protein like 1 NSP like
protein 1 NSPLI Homo sapiens Human
Chondroitin sulfate glucuronyltransferase EC 2 4 1 226 N
acetylgalactosaminyl proteoglycan 3 beta glucuronosyltransferase Chondroitin glucuronyltransferase II CSGlcA T Homo
sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
40S ribosomal protein S12 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
ER degradation enhancing alpha mannosidase like 1 Homo
sapiens Human
ER degradation enhancing alpha mannosidase like 1 Homo
sapiens Human
Zinc finger BED domain containing protein 4 Homo sapiens
Human
Killer cell immunoglobulin like receptor 2DL2 precursor
MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43
p58 NK receptor Homo sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Prolactin regulatory element binding protein Mammalian guanine nucleotide exchange factor mSec12 Homo sapiens Human
Reticulon-2 Neuroendocrine specific protein like 1 NSP like
protein 1 NSPLI Homo sapiens Human
Ras-related protein Ral B Homo sapiens Human
Putative ATP dependent RNA helicase DHX33 EC 3 6 1
DEAH box protein 33 Homo sapiens Human
Frizzled-2 precursor Fz 2 hFz2 FzE2 Homo sapiens Human
208
3.08
L-myc-1 proto oncogene protein Homo sapiens Human
13129
13149
12871
12898
12842
13038
12906
12983
12976
13033
13050
13050
12848
13088
12865
13140
13095
13152
12905
13035
13122
238
1
2
3
4
209
3.07
13032
210
3.07
211
3.06
212
3.06
213
3.05
214
2.92
215
2.91
216
217
2.85
2.83
218
2.81
219
2.79
220
2.79
221
222
2.76
2.72
223
2.71
224
2.59
225
2.58
226
227
2.57
2.56
228
229
2.50
2.49
230
2.44
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Vacuolar protein sorting associated protein 25 hVps25 ELL
associated protein of 20 kDa Dermal papilla derived protein 9
Homo sapiens Human
Vacuolar protein sorting associated protein 25 hVps25 ELL
associated protein of 20 kDa Dermal papilla derived protein 9
Homo sapiens Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Actin-binding Rho activating protein Striated muscle activator
of Rho dependent signaling STARS Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Cystatin-S precursor Cystatin 4 Salivary acidic protein 1 Cystatin SA III Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Protein mago nashi homolog Homo sapiens Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo
sapiens Human
Arachidonate 15 lipoxygenase type II EC 1 13 11 33 15 LOX
2 15 lipoxygenase 2 Homo sapiens Human
Testis-expressed sequence 10 protein Homo sapiens Human
Nuclear pore complex protein Nup153 Nucleoporin Nup153
153 kDa nucleoporin Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Presequence protease mitochondrial precursor EC 3 4 24
hPreP Pitrilysin metalloproteinase 1 Metalloprotease 1 hMP1
Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
13032
12943
12943
13069
13055
13044
12973
12899
13206
12866
12866
13042
12893
13098
12974
13156
13159
13058
12965
12875
12950
239
1
2
3
4
231
2.41
13022
232
2.41
233
234
235
236
2.40
2.40
2.38
2.37
237
2.35
238
239
240
2.33
2.33
2.26
241
2.22
242
2.22
243
2.21
244
245
246
2.18
2.18
2.14
247
2.08
248
2.05
249
2.03
250
2.03
251
252
2.01
1.90
253
1.87
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Olfactory receptor 10A7 Olfactory receptor OR12 6 Homo
sapiens Human
Angiopoietin-1 precursor ANG 1 Homo sapiens Human
Angiopoietin-1 precursor ANG 1 Homo sapiens Human
Olfactory receptor 52E2 Homo sapiens Human
Transcription factor AP 2 alpha AP2 alpha Activating enhancer binding protein 2 alpha AP 2 transcription factor Activator
protein 2 AP 2 Homo sapiens Human
Killer cell immunoglobulin like receptor 2DL2 precursor
MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43
p58 NK receptor Homo sapiens Human
Nucleolar protein 66 hsNO66 Homo sapiens Human
Nucleolar protein 66 hsNO66 Homo sapiens Human
Nucleolar protein NOP5 Nucleolar protein 5 NOP58 Homo
sapiens Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Regenerating islet derived protein 4 precursor Reg IV REG
like protein Gastrointestinal secretory protein Homo sapiens
Human
Protein yippee like 4 Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
Trefoil factor 3 precursor Intestinal trefoil factor hP1 B Homo
sapiens Human
Germinal center B cell expressed transcript 2 protein Germinal
center associated lymphoma protein hGAL Homo sapiens
Human
Cadherin-like protein 26 precursor Cadherin like protein VR20
Homo sapiens Human
Zinc finger BED domain containing protein 4 Homo sapiens
Human
Zinc finger BED domain containing protein 4 Homo sapiens
Human
Secretagogin Homo sapiens Human
Killer cell immunoglobulin like receptor 2DL2 precursor
MHC class I NK cell receptor Natural killer associated transcript 6 NKAT 6 p58 natural killer cell receptor clone CL 43
p58 NK receptor Homo sapiens Human
Uncharacterized protein C1orf50 Homo sapiens Human
13022
12850
12850
12994
13207
13161
13045
13045
13144
13021
13021
13075
12806
12806
13008
13143
12886
12882
12882
12873
13139
13062
240
1
2
3
4
254
1.86
12843
255
1.83
256
1.79
257
1.76
258
1.76
259
1.74
260
1.73
261
1.65
262
1.63
263
1.62
264
1.58
265
1.52
266
1.51
267
268
269
1.50
1.50
1.48
270
1.47
271
1.44
272
1.41
273
1.38
274
275
276
1.32
1.27
1.26
YTH domain containing protein 1 Putative splicing factor
YT521 Homo sapiens Human
HLA class II histocompatibility antigen DM beta chain precursor MHC class II antigen DMB Homo sapiens Human
Selenocysteine-specific elongation factor Elongation factor sec
Eukaryotic elongation factor selenocysteine tRNA specific
Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4
6 tetrakisphosphate 5 kinase Homo sapiens Human
Inositol polyphosphate multikinase EC 2 7 1 151 Inositol 1 3 4
6 tetrakisphosphate 5 kinase Homo sapiens Human
Complex I intermediate associated protein 30 mitochondrial
precursor NADH dehydrogenase ubiquinone 1 alpha subcomplex assembly factor 1 Homo sapiens Human
Oligodendrocyte transcription factor 1 Oligo1 Homo sapiens
Human
Arachidonate 15 lipoxygenase type II EC 1 13 11 33 15 LOX
2 15 lipoxygenase 2 Homo sapiens Human
Methionyl-tRNA synthetase cytoplasmic EC 6 1 1 10 Methionine tRNA ligase MetRS Homo sapiens Human
Cadherin-like protein 26 precursor Cadherin like protein VR20
Homo sapiens Human
HLA class II histocompatibility antigen DM beta chain precursor MHC class II antigen DMB Homo sapiens Human
Ladinin 1 Lad 1 120 kDa linear IgA bullous dermatosis antigen 97 kDa linear IgA bullous dermatosis antigen Linear IgA
disease antigen homolog LadA Homo sapiens Human
Serine/threonine-protein kinase Pim 3 EC 2 7 11 1 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
Keratin-associated protein 21 2 Homo sapiens Human
E3 ubiquitin protein ligase RNF19 EC 6 3 2 RING finger protein 19 Dorfin Double ring finger protein p38 protein Homo
sapiens Human
Transmembrane gamma carboxyglutamic acid protein 1 precursor Proline rich Gla protein 1 Proline rich gamma carboxyglutamic acid protein 1 Homo sapiens Human
Arachidonate 15 lipoxygenase type II EC 1 13 11 33 15 LOX
2 15 lipoxygenase 2 Homo sapiens Human
Acyl-CoA-binding domain containing protein 7 Homo sapiens
Human
Elongation factor Tu mitochondrial precursor EF Tu P43 Homo sapiens Human
Oncostatin-M precursor OSM Homo sapiens Human
Protein yippee like 4 Homo sapiens Human
UPF0318 protein FAM120A Homo sapiens Human
13163
12861
13097
13097
13012
12841
12928
13079
13009
13089
12854
13100
12992
12992
12851
13052
12917
13001
13133
13171
13006
12919
241
1
2
3
4
277
1.23
12856
278
1.18
279
1.07
280
1.05
281
0.99
282
0.94
283
284
0.86
0.84
285
0.63
286
0.62
287
0.62
288
0.59
289
0.54
290
0.48
Steroidogenic acute regulatory protein mitochondrial precursor
StAR StARD1 Homo sapiens Human
Breast carcinoma amplified sequence 1 Novel amplified in
breast cancer 1 Amplified and overexpressed in breast cancer
Homo sapiens Human
Syntaxin-binding protein 1 Unc 18 homolog Unc 18A Unc 18
1 N Sec1 p67 Homo sapiens Human
Guanylyl cyclase activating protein 3 GCAP 3 Guanylate cyclase activator 1C Homo sapiens Human
Glypican-3 precursor Intestinal protein OCI 5 GTR2 2 MXR7
Homo sapiens Human
Zinc finger protein 148 Zinc finger DNA binding protein 89
Transcription factor ZBP 89 Homo sapiens Human
Protein Dom3Z Dom 3 homolog Z Homo sapiens Human
Desmoglein-3 precursor 130 kDa pemphigus vulgaris antigen
PVA Homo sapiens Human
Protein transport protein Sec24D SEC24 related protein D
Homo sapiens Human
Aldehyde dehydrogenase dimeric NADP preferring EC 1 2 1 5
ALDH class 3 ALDHIII Homo sapiens Human
Aldehyde dehydrogenase dimeric NADP preferring EC 1 2 1 5
ALDH class 3 ALDHIII Homo sapiens Human
Protein arginine N methyltransferase 6 EC 2 1 1 Heterogeneous nuclear ribonucleoprotein methyltransferase like protein 6
Homo sapiens Human
Cyclin-dependent kinases regulatory subunit 1 CKS 1 Homo
sapiens Human
Dickkopf-like protein 1 precursor Soggy 1 protein SGY 1
Homo sapiens Human
13199
13099
12985
13150
13072
12915
12930
13103
13068
13068
12980
13157
12993
242
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