Whsc1 links pluripotency exit with mesendoderm specification
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- dc.contributor.author Tian, Tian V.
- dc.contributor.author Di Stefano, Bruno, 1984-
- dc.contributor.author Stik, Grégoire
- dc.contributor.author Vila-Casadesús, Maria
- dc.contributor.author Sardina, Jose Luis
- dc.contributor.author Vidal Ocabo, Enrique
- dc.contributor.author Dasti, Alessandro, 1988-
- dc.contributor.author Segura-Morales, Carolina
- dc.contributor.author de Andrés-Aguayo, Luisa
- dc.contributor.author Gómez, Antonio
- dc.contributor.author Goldmann, Johanna
- dc.contributor.author Jaenisch, Rudolf
- dc.contributor.author Graf, T. (Thomas)
- dc.date.accessioned 2021-02-19T09:36:49Z
- dc.date.available 2021-02-19T09:36:49Z
- dc.date.issued 2019
- dc.description.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.
- dc.description.sponsorship J.L.S. were supported by Juan de la Cierva postdoctoral fellowships (MINECO; FJCI-2014-22946 and IJCI-2014-21872), B.D.S. by an EMBO long-term fellowship (number ALTF 1143-2015), G.S. by a Marie Sklodowska-Curie fellowship (H2020-MSCA-IF-2016, miRStem), A.D. by a Severo Ochoa fellowship and J.G. by a Boehringer Ingelheim Graduate Student Fellowship. R.J. was supported by NIH grants R01 NS088538-01 and 2R01MH104610-15. This work was supported by the EU-FP7 project BLUEPRINT, the Spanish Ministry of Economy, Industry and Competitiveness to the EMBL partnership, Centro de Excelencia Severo Ochoa 2013–2017 and the CERCA Program Generalitat de Catalunya. T.V.T., J.L.S. and B.D.S. were supported by a CRG award for junior collaborative projects
- dc.format.mimetype application/pdf
- dc.identifier.citation Tian TV, Di Stefano B, Stik G, Vila-Casadesus M, Sardina JL, Vidal E et al. Whsc1 links pluripotency exit with mesendoderm specification. Nat Cell Biol. 2019 Jul; 21(7): 824-834. DOI: 10.1038/s41556-019-0342-1
- dc.identifier.doi http://dx.doi.org/10.1038/s41556-019-0342-1
- dc.identifier.issn 1465-7392
- dc.identifier.uri http://hdl.handle.net/10230/46545
- dc.language.iso eng
- dc.publisher Nature Research
- dc.relation.ispartof Nature Cell Biology. 2019 Jul; 21(7): 824-34
- dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/282510
- dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/747539
- dc.rights © Tian V. Tian et al, under exclusive licence to Springer Nature Limited 2019
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.subject.other Biologia del desenvolupament
- dc.subject.other Genètica
- dc.subject.other Proteïnes
- dc.subject.other Enzims
- dc.title Whsc1 links pluripotency exit with mesendoderm specification
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/acceptedVersion