Article ID Journal Published Year Pages File Type
2093401 Stem Cell Reports 2015 9 Pages PDF
Abstract

•Klf2 and Tfcp2l1 are downstream targets of Wnt/β-catenin•Klf2 and Tfcp2l1 overexpression maintains mESC self-renewal•Downregulation of Klf2 and Tfcp2l1 impairs mESC self-renewal mediated by 2i•KLF2 and TFCP2L1 promote reprogramming of EpiSCs to naive ESCs

SummaryActivation 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.

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