TFAP2C facilitates somatic cell reprogramming by inhibitingc-Myc-dependent apoptosis and promoting mesenchymal-to-epithelial transition

Transcription factors are known to mediate the conversion of somatic cells to induced pluripotent stem cells (iPSCs). Transcription factor TFAP2C plays important roles in the regulation of embryonic development and carcinogenesis; however, the roles ofTfap2cin regulating somatic cell reprogramming are not well understood. Here we demonstrateTfap2cis induced during the generation of iPSCs from mouse fibroblasts and acts as a facilitator for iPSCs formation. Mechanistically, thec-Myc-dependent apoptosis, which is a roadblock to reprogramming, can be significantly mitigated byTfap2coverexpression. Meanwhile,Tfap2ccan greatly promote mesenchymal-to-epithelial transition (MET) at initiation stage of OSKM-induced reprogramming. Further analysis of gene expression and targets ofTfap2cduring reprogramming by RNA-sequencing (RNA-seq) and ChIP-qPCR indicates that TFAP2C can promote epithelial gene expression by binding to their promoters directly. Finally, knockdown ofE-cadherin(Cdh1), an important downstream target of TFAP2C and a critical regulator of MET antagonizesTfap2c-mediated reprogramming. Taken together, we conclude thatTfap2cserves as a strong activator for somatic cell reprogramming through promoting the MET and inhibitingc-Myc-dependent apoptosis.