MiR‐134‐Mbd3 axis regulates the induction of pluripotency

MicroRNAs (miRNAs) are post‐transcriptional modulators of gene expression and play an important role in reprogramming process; however, relatively little is known about the underlying regulatory mechanism of miRNAs on how they epigenetically modulate reprogramming and pluripotency. Here, we report that the expression level of microRNA‐134 (miR‐134) was low in mouse embryonic stem cells (mESCs) but significantly up‐regulated during neural differentiation, while down‐regulated during the induction of induced pluripotent stem cells (iPSCs) from neural progenitor cells (NPCs). Inhibition of miR‐134 by miR‐134 sponge promoted the efficiency of reprogramming which also was highly similar to mESCs. On the contrary, up‐regulation of miR‐134 repressed iPSCs induction. We also found that inhibition of miR‐134 promoted the maturation of pre‐iPSCs and increased its pluripotency. We also showed that miR‐134 can directly target to the pluripotency related factor Methyl‐CpG‐binding domain protein 3 (Mdb3) 3′ untranslated regions (3′ UTR) to down‐regulate its expression. And Mbd3 was found to promote the induction of iPSCs and could block the repression of reprogramming caused by overexpression of miR‐134. This work revealed the critical function of miR‐134‐Mbd3 axis on regulating reprogramming and pluripotency of iPSCs derived from the NPCs, and might provide an insight into the miR‐134‐Mbd3 axis on regulating the iPSCs quality for further clinical treatment.