Forkhead box family transcription factors as versatile regulators for cellular reprogramming to pluripotency

叉头框家族转录因子作为细胞重编程至多能性的多功能调节剂

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作者:Meijun Fu #, Huan Chen #, Zepo Cai, Yihang Yang, Ziyu Feng, Mengying Zeng, Lijun Chen, Yue Qin, Baomei Cai, Pinghui Zhu, Chunhua Zhou, Shengyong Yu, Jing Guo, Jing Liu, Shangtao Cao, Duanqing Pei

Abstract

Forkhead box (Fox) transcription factors play important roles in mammalian development and disease. However, their function in mouse somatic cell reprogramming remains unclear. Here, we report that FoxD subfamily and FoxG1 accelerate induced pluripotent stem cells (iPSCs) generation from mouse fibroblasts as early as day4 while FoxA and FoxO subfamily impede this process obviously. More importantly, FoxD3, FoxD4 and FoxG1 can replace Oct4 respectively and generate iPSCs with germline transmission together with Sox2 and Klf4. On the contrary, FoxO6 almost totally blocks reprogramming through inhibiting cell proliferation, suppressing the expression of pluripotent genes and hindering the process of mesenchymal to epithelial transition (MET). Thus, our study uncovers unexpected roles of Fox transcription factors in reprogramming and offers new insights into cell fate transition.

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