title: Depletion ofTcf3andLef1maintains mouse embryonic stem cell self-renewal.
abstract: 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 ofLef1partially mimics the self-renewal-promoting effect of MEK inhibitors. Moreover, depletion of bothTcf3andLef1enables 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.
authors.affiliation: 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.
authors.forename: Shoudong
authors.initials: S
authors.lastname: Ye
authors.affiliation: Center for Stem Cell and Translational Medicine, School of Life Sciences, Anhui University, Hefei 230601, People's Republic of China.
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Chang
authors.initials: C
authors.lastname: Tong
authors.affiliation: 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.
authors.forename: Xingliang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Center for Stem Cell and Translational Medicine, School of Life Sciences, Anhui University, Hefei 230601, People's Republic of China.
authors.forename: Kan
authors.initials: K
authors.lastname: He
authors.affiliation: Center for Stem Cell and Translational Medicine, School of Life Sciences, Anhui University, Hefei 230601, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Ban
authors.affiliation: Center for Stem Cell and Translational Medicine, School of Life Sciences, Anhui University, Hefei 230601, People's Republic of China seanstem@126.com qying@med.usc.edu.
authors.forename: Dahai
authors.identifier: http://orcid.org/0000-0001-6201-9776
authors.initials: D
authors.lastname: Liu
authors.affiliation: 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 seanstem@126.com qying@med.usc.edu.
authors.forename: Qi-Long
authors.initials: QL
authors.lastname: Ying
keywords: Differentiation; Embryonic stem cells; LEF1; Self-renewal; TCF3