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

TitleEmbryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells.
Publication TypeJournal Article
Year of Publication2011
Authorsten Berge D, Kurek D, Blauwkamp T, Koole W, Maas A, Eroglu E, Siu RK, Nusse R
JournalNature cell biology
Volume13
Issue9
Pagination1070-5
Date Published2011 Aug 14
ISSN1465-7392
AbstractPluripotent 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.
URLhttp://dx.doi.org/10.1038/ncb2314
DOI10.1038/ncb2314
Short TitleNat Cell Biol