Whsc1 links pluripotency exit with mesendoderm specification
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...
| Main Authors: | , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2019
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| Online Access: | https://hdl.handle.net/1721.1/121965 |
| _version_ | 1811076225175650304 |
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| author | 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 Goldmann, Johanna Jaenisch, Rudolf Graf, Thomas |
| author2 | Whitehead Institute for Biomedical Research |
| author_facet | Whitehead Institute for Biomedical Research 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 Goldmann, Johanna Jaenisch, Rudolf Graf, Thomas |
| author_sort | Tian, Tian V. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T10:18:16Z |
| format | Article |
| id | mit-1721.1/121965 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T10:18:16Z |
| publishDate | 2019 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1219652024-06-24T18:48:30Z Whsc1 links pluripotency exit with mesendoderm specification 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 Goldmann, Johanna Jaenisch, Rudolf Graf, Thomas Whitehead Institute for Biomedical Research Cell Biology 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. 2019-08-02T19:22:08Z 2019-08-02T19:22:08Z 2019-06 2017-07 2019-08-02T18:23:52Z Article http://purl.org/eprint/type/JournalArticle 1465-7392 1476-4679 https://hdl.handle.net/1721.1/121965 Tian, Tian V. et al. "Whsc1 links pluripotency exit with mesendoderm specification." Nature Cell Biology 21 (June 2019): 824-834 © 2019 The Author(s) en http://dx.doi.org/10.1038/s41556-019-0342-1 Nature Cell Biology 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. application/pdf Springer Science and Business Media LLC Prof. Rudolf Jaenisch |
| spellingShingle | Cell Biology 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 Goldmann, Johanna Jaenisch, Rudolf Graf, Thomas Whsc1 links pluripotency exit with mesendoderm specification |
| title | Whsc1 links pluripotency exit with mesendoderm specification |
| title_full | Whsc1 links pluripotency exit with mesendoderm specification |
| title_fullStr | Whsc1 links pluripotency exit with mesendoderm specification |
| title_full_unstemmed | Whsc1 links pluripotency exit with mesendoderm specification |
| title_short | Whsc1 links pluripotency exit with mesendoderm specification |
| title_sort | whsc1 links pluripotency exit with mesendoderm specification |
| topic | Cell Biology |
| url | https://hdl.handle.net/1721.1/121965 |
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