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

Abstract

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.

• Authors: Yuan Wang, Shuang Chen, Qingyuan Jiang, Jie Deng, Fuyi Cheng, Yi Lin, Lin Cheng, Yixin Ye, Xiaolei Chen, Yunqi Yao, Xiaomei Zhang, Gang Shi, Lei Dai, Xiaolan Su, Yong Peng, Hongxin Deng
• Journal: Cell death & disease (Cell Death Dis) Vol. 11 Issue 6 Pg. 482 (06 25 2020) ISSN: 2041-4889 [Electronic] England
• PMID: 32587258 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Proto-Oncogene Proteins c-myc
• Tfap2c protein, mouse
• Transcription Factor AP-2

Topics

• Animals
• Apoptosis (genetics)
• Base Sequence
• Cellular Reprogramming (genetics)
• Epithelial-Mesenchymal Transition (genetics)
• HEK293 Cells
• Humans
• Induced Pluripotent Stem Cells (metabolism)
• Mice, Inbred C57BL
• Mice, Transgenic
• Proto-Oncogene Proteins c-myc (metabolism)
• Transcription Factor AP-2 (metabolism)
• Up-Regulation (genetics)