Author: ["Derk ten Berge","Dorota Kurek","Tim Blauwkamp","Wouter Koole","Alex Maas","Elif Eroglu","Ronald K. Siu","Roel Nusse"]
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Abstract
ten Berge and colleagues show that Wnt signalling is required for self-renewal of embryonic stem cells through inhibition of their differentiation into epiblast stem cells. Together, Wnt and LIF signalling can support derivation and self-renewal of embryonic stem cells. 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 marks2. In contrast, EpiSCs have activated the epigenetic machinery that supports differentiation towards the embryonic cell types3,4,5,6. 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.Cite this article
ten Berge, D., Kurek, D., Blauwkamp, T. et al. Embryonic stem cells require Wnt proteins to prevent differentiation to epiblast stem cells. Nat Cell Biol 13, 1070–1075 (2011). https://doi.org/10.1038/ncb2314 