title: Klf2 and Tfcp2l1, Two Wnt/β-Catenin Targets, Act Synergistically to Induce and Maintain Naive Pluripotency.
abstract: Activation of Wnt/β-catenin signaling can induce both self-renewal and differentiation in naive pluripotent embryonic stem cells (ESCs). To gain insights into the mechanism by which Wnt/β-catenin regulates ESC fate, we screened and characterized its downstream targets. Here, we show that the self-renewal-promoting effect of Wnt/β-catenin signaling is mainly mediated by two of its downstream targets, Klf2 and Tfcp2l1. Forced expression of Klf2 and Tfcp2l1 can not only induce reprogramming of primed state pluripotency into naive state ESCs, but also is sufficient to maintain the naive pluripotent state of ESCs. Conversely, downregulation of Klf2 and Tfcp2l1 impairs ESC self-renewal mediated by Wnt/β-catenin signaling. Our study therefore establishes the pivotal role of Klf2 and Tfcp2l1 in mediating ESC self-renewal promoted by Wnt/β-catenin signaling.
authors: Guangdong Provincial Key Laboratory of Liver Disease, Cell-Gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, PRC; Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, University of Southern California, Los Angeles, CA 90033, USA.
authors: Dongbo
authors: D
authors: Qiu
authors: Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, University of Southern California, Los Angeles, CA 90033, USA; Center for Stem Cell and Translational Medicine, School of Life Sciences, Anhui University, Hefei 230601, PRC.
authors: Shoudong
authors: S
authors: Ye
authors: Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, University of Southern California, Los Angeles, CA 90033, USA.
authors: Bryan
authors: B
authors: Ruiz
authors: Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, University of Southern California, Los Angeles, CA 90033, USA.
authors: Xingliang
authors: X
authors: Zhou
authors: Center for Stem Cell and Translational Medicine, School of Life Sciences, Anhui University, Hefei 230601, PRC.
authors: Dahai
authors: D
authors: Liu
authors: Guangdong Provincial Key Laboratory of Liver Disease, Cell-Gene Therapy Translational Medicine Research Center, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, PRC.
authors: Qi
authors: Q
authors: Zhang
authors: Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC, University of Southern California, Los Angeles, CA 90033, USA. Electronic address: qying@med.usc.edu.
authors: Qi-Long
authors: QL
authors: Ying
mesh_terms: D000818:Animals; D015536:Down-Regulation; D051741:Kruppel-Like Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C498314:Klf2 protein, mouse; D051741:Kruppel-Like Transcription Factors; D012097:Repressor Proteins; C486070:Tfcp2l1 protein, mouse; D051176:beta Catenin