Whsc1 links pluripotency exit with mesendoderm specification
Name
Tian et al. Ms.pdf
Description
Accepted version
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274.67 KB
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Author(s)
Tian, Tian V.
Di Stefano, Bruno
Stik, Grégoire
Vila-Casadesús, Maria
Sardina, José Luis
Vidal, Enrique
Dasti, Alessandro
Segura-Morales, Carolina
De Andrés-Aguayo, Luisa
Gómez, Antonio
Date Issued
June 2019
Journal
Nature Cell Biology
Publisher
Springer Science and Business Media LLC
Citation
Tian, Tian V. et al. "Whsc1 links pluripotency exit with mesendoderm specification." Nature Cell Biology 21 (June 2019): 824-834 © 2019 The Author(s)
Version
Author's final manuscript
Abstract
How pluripotent stem cells differentiate into the main germ layers is a key question of developmental biology. Here, we show that the chromatin-related factor Whsc1 (also known as Nsd2 and MMSET) has a dual role in pluripotency exit and germ layer specification of embryonic stem cells. On induction of differentiation, a proportion of Whsc1-depleted embryonic stem cells remain entrapped in a pluripotent state and fail to form mesendoderm, although they are still capable of generating neuroectoderm. These functions of Whsc1 are independent of its methyltransferase activity. Whsc1 binds to enhancers of the mesendodermal regulators Gata4, T (Brachyury), Gata6 and Foxa2, together with Brd4, and activates the expression of these genes. Depleting each of these regulators also delays pluripotency exit, suggesting that they mediate the effects observed with Whsc1. Our data indicate that Whsc1 links silencing of the pluripotency regulatory network with activation of mesendoderm lineages.
Subjects
Cell Biology
MIT Department
Whitehead Institute for Biomedical Research
Terms of Use
Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/s41556-019-0342-1
