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

Author:

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

Abstract

AbstractForkhead 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.

Funder

Innovative Research Group Project of the National Natural Science Foundation of China

Major State Basic Research Development Program

National Natural Science Foundation of China

National Basic Research Program of China (973 Program)

Science and Technology Planning Project of Guangdong Province

Publisher

Springer Science and Business Media LLC

Subject

Cell Biology,Developmental Biology

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