Whsc1 Links Pluripotency Exit With Mesendoderm Specification

 
Thumbnail
View/Open
Manuscript (52.63Mb)
Access Status
Full text of the requested work is not available in DASH at this time ("restricted access"). For more information on restricted deposits, see our FAQ.
Author
Stik, Grégoire
Vila-Casadesús, Maria
Sardina, José Luis
Vidal, Enrique
Dasti, Alessandro
Segura Morales, Carolina
De Andres Aguayo, Luisa
Gomez, Antonio
Goldmann, Johanna
Jaenisch, Rudolf
Graf, Thomas
Tian, Tian
Jaenisch, Rudolf
Metadata
Show full item record
Citation
Tian, Tian V., Bruno Di Stefano, Grégoire Stik, Maria Vila-Casadesús, José Luis Sardina, Enrique Vidal, Alessandro Dasti, Carolina Segura-Morales, Luisa De Andrés-Aguayo, Antonio Gómez, Johanna Goldmann, Rudolf Jaenisch, and Thomas Graf. 2019. Whsc1 Links Pluripotency Exit with Mesendoderm Specification. Nature Cell Biology 21, no. 7: 824-34.
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 (Nsd2, MMSET) has a dual role in pluripotency exit and germ layer specification of embryonic stem cells (ESCs). Upon induction of differentiation, a proportion of Whsc1-depleted ESCs 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 genes’ expression. 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.
Citable link to this page
https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37374212

Collections