REBIRTH-Group Reprogramming, Hannover Medical School, 30625 Hannover, Germany.
EMBO Rep. 2011 Oct 28;12(11):1153-9. doi: 10.1038/embor.2011.176.
Induced pluripotent stem cells (iPSCs) can be generated by overexpression of Oct4, Sox2 and Klf4 in murine fibroblasts. By conducting a microRNA (miRNA) library screen, we identified a set of miRNAs critically regulating iPSC formation. We revealed a new miRNA family (miR-130/301/721) as an important regulator of iPSC induction by targeting the homeobox transcription factor Meox2 (also known as Gax). Meox2-specific silencing mimicked the effects of this miRNA family on reprogramming. Mechanistically, miRNA-resistant Meox2 overexpression abrogated effects of miR-130/301/721 on reprogramming. In conclusion, the miRNA family miR-130/301/721 enhances iPSC generation via repression of Meox2.
诱导多能干细胞(iPSCs)可通过在鼠成纤维细胞中过表达 Oct4、Sox2 和 Klf4 来生成。通过进行 microRNA(miRNA)文库筛选,我们鉴定出一组 miRNA 对 iPSC 形成具有关键调控作用。我们揭示了一个新的 miRNA 家族(miR-130/301/721)作为 iPSC 诱导的重要调节剂,通过靶向同源盒转录因子 Meox2(也称为 Gax)发挥作用。Meox2 特异性沉默模拟了该 miRNA 家族对重编程的作用。从机制上讲,miRNA 抗性 Meox2 过表达消除了 miR-130/301/721 对重编程的影响。总之,miRNA 家族 miR-130/301/721 通过抑制 Meox2 增强 iPSC 的生成。