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Snail1-dependent control of embryonic stem cell pluripotency and lineage commitment

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  • Yongshun Lin

    (Life Sciences Institute, University of Michigan
    Center for Molecular Medicine, National Heart, Lung and Blood Institute)

  • Xiao-Yan Li

    (Life Sciences Institute, University of Michigan)

  • Amanda L. Willis

    (Life Sciences Institute, University of Michigan)

  • Chengyu Liu

    (Center for Molecular Medicine, National Heart, Lung and Blood Institute)

  • Guokai Chen

    (Center for Molecular Medicine, National Heart, Lung and Blood Institute)

  • Stephen J. Weiss

    (Life Sciences Institute, University of Michigan)

Abstract

Embryonic stem cells (ESCs) exhibit the dual properties of self-renewal and pluripotency as well as the ability to undergo differentiation that gives rise to all three germ layers. Wnt family members can both promote ESC maintenance and trigger differentiation while also controlling the expression of Snail1, a zinc-finger transcriptional repressor. Snail1 has been linked to events ranging from cell cycle regulation and cell survival to epithelial–mesenchymal transition (EMT) and gastrulation, but its role in self-renewal, pluripotency or lineage commitment in ESCs remains undefined. Here we demonstrate using isogenic pairs of conditional knockout mouse ESCs, that Snail1 exerts Wnt- and EMT independent control over the stem cell transcriptome without affecting self-renewal or pluripotency-associated functions. By contrast, during ESC differentiation, an endogenous Wnt-mediated burst in Snail1 expression regulates neuroectodermal fate while playing a required role in epiblast stem cell exit and the consequent lineage fate decisions that define mesoderm commitment.

Suggested Citation

  • Yongshun Lin & Xiao-Yan Li & Amanda L. Willis & Chengyu Liu & Guokai Chen & Stephen J. Weiss, 2014. "Snail1-dependent control of embryonic stem cell pluripotency and lineage commitment," Nature Communications, Nature, vol. 5(1), pages 1-14, May.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4070
    DOI: 10.1038/ncomms4070
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