miRNA screening reveals a new miRNA family stimulating iPS cell generation via regulation of Meox2

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.