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 of Tfap2c in regulating somatic cell reprogramming are not well understood. Here we demonstrate Tfap2c is induced during the generation of iPSCs from mouse fibroblasts and acts as a facilitator for iPSCs formation. Mechanistically, the c-Myc-dependent apoptosis, which is a roadblock to reprogramming, can be significantly mitigated by Tfap2c overexpression. Meanwhile, Tfap2c can greatly promote mesenchymal-to-epithelial transition (MET) at initiation stage of OSKM-induced reprogramming. Further analysis of gene expression and targets of Tfap2c during 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 of E-cadherin (Cdh1), an important downstream target of TFAP2C and a critical regulator of MET antagonizes Tfap2c-mediated reprogramming. Taken together, we conclude that Tfap2c serves as a strong activator for somatic cell reprogramming through promoting the MET and inhibiting c-Myc-dependent apoptosis.

已知转录因子介导体细胞向诱导多能干细胞（iPSC）的转化。转录因子TFAP2C在调节胚胎发育和致癌作用中起着重要作用。但是，Tfap2c在调节体细胞重编程中的作用尚不十分清楚。在这里，我们证明Tfap2c在小鼠成纤维细胞产生iPSC的过程中被诱导，并充当iPSCs形成的促进剂。从机制上讲，Tfap2c过表达可以显着缓解c-Myc依赖性细胞凋亡，这是重编程的障碍。同时，Tfap2c可以在OSKM诱导的重编程起始阶段极大地促进间质到上皮的转化（MET）。通过RNA测序（RNA-seq）和ChIP-qPCR在重编程过程中进一步分析Tfap2c的基因表达和靶标，表明TFAP2C可通过直接结合其启动子来促进上皮基因表达。最后，敲低E-钙粘蛋白（Cdh1），TFAP2C的重要下游靶标和MET的关键调节剂拮抗Tfap2c介导的重编程。两者合计，我们得出结论，Tfap2c通过促进MET和抑制c-Myc依赖性细胞凋亡而成为体细胞重编程的强激活剂。