Depletion of Tcf3 and Lef1 maintains mouse embryonic stem cell self-renewal

Biology Open

Kan He¹  Qian Ban¹  Shoudong Ye¹  Tao Zhang¹  Dahai Liu¹  Xingliang Zhou²  Qi-Long Ying²  Chang Tong² 

[1] Center for Stem Cell and Translational Medicine, School of Life Sciences, Anhui University, Hefei 230601, People's Republic of China;Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA;

关键词: Differentiation;    Embryonic stem cells;    LEF1;    Self-renewal;    TCF3;   

DOI  :  10.1242/bio.022426

来源: DOAJ

【 摘 要 】

Mouse and rat embryonic stem cell (ESC) self-renewal can be maintained by dual inhibition of glycogen synthase kinase 3 (GSK3) and mitogen-activated protein kinase kinase (MEK). Inhibition of GSK3 promotes ESC self-renewal by abrogating T-cell factor 3 (TCF3)-mediated repression of the pluripotency network. How inhibition of MEK mediates ESC self-renewal, however, remains largely unknown. Here, we show that inhibition of MEK can significantly suppress lymphoid enhancer factor 1 (LEF1) expression in mouse ESCs. Knockdown or knockout of Lef1 partially mimics the self-renewal-promoting effect of MEK inhibitors. Moreover, depletion of both Tcf3 and Lef1 enables maintenance of undifferentiated mouse ESCs without exogenous factors, cytokines or inhibitors. Transcriptome resequencing analysis reveals that LEF1 is closely associated with endoderm specification in ESCs. Thus, our study adds support to the notion that the key to maintaining the ESC ground state is to shield ESCs from differentiative cues.

【 授权许可】

Unknown