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Nat Cell Biol. 2011 Aug 14;13(9):1070-5. doi: 10.1038/ncb2314.

Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells.

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  • 1Erasmus MC Stem Cell Institute, Department of Cell Biology, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. d.tenberge@erasmusmc.nl

Abstract

Pluripotent stem cells exist in naive and primed states, epitomized by mouse embryonic stem cells (ESCs) and the developmentally more advanced epiblast stem cells (EpiSCs; ref. 1). In the naive state of ESCs, the genome has an unusual open conformation and possesses a minimum of repressive epigenetic marks. In contrast, EpiSCs have activated the epigenetic machinery that supports differentiation towards the embryonic cell types. The transition from naive to primed pluripotency therefore represents a pivotal event in cellular differentiation. But the signals that control this fundamental differentiation step remain unclear. We show here that paracrine and autocrine Wnt signals are essential self-renewal factors for ESCs, and are required to inhibit their differentiation into EpiSCs. Moreover, we find that Wnt proteins in combination with the cytokine LIF are sufficient to support ESC self-renewal in the absence of any undefined factors, and support the derivation of new ESC lines, including ones from non-permissive mouse strains. Our results not only demonstrate that Wnt signals regulate the naive-to-primed pluripotency transition, but also identify Wnt as an essential and limiting ESC self-renewal factor.

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PMID:
21841791
[PubMed - indexed for MEDLINE]
PMCID:
PMC4157727
Free PMC Article
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