The combined action of Esrrb and Nr5a2 is essential for murine naïve pluripotency
| Autor: | Festuccia, Nicola, Owens, Nick, Chervova, Almira, Dubois, Agnès, Navarro, Pablo |
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| Přispěvatelé: | Epigénomique, Prolifération et Identité Cellulaire - Epigenomics, Proliferation and the Identity of Cells (EPIC), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Imperial College London, University of Exeter Medical School, University of Exeter, N.F., during his stay at the LMS, was funded by an Imperial College London Research Fellowship and a Medical Research Council Career Development Award. P.N. acknowledges the European Research Council (Erc-cog-2017, BIND), the Labex Revive (Investissement d'Avenir, ANR-10-LABX-73), the Institut Pasteur and the Centre National de la Recherche Scientifique for funding. Deposited in PMC for immediate release., We thank the MRC London Institute of Medical Sciences flow cytometry and microscopy facilities for providing technical assistance., ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Pluripotency
Embryonic stem cells Orphan nuclear receptors [SDV]Life Sciences [q-bio] SOXB1 Transcription Factors Stem Cells & Regeneration Receptors Cytoplasmic and Nuclear Cell Differentiation Mouse Embryonic Stem Cells Nanog Homeobox Protein Stem Cells and Regeneration Mice Receptors Estrogen Nr5a2 embryonic structures Animals Gene Regulatory Networks biological phenomena cell phenomena and immunity Esrrb Cell Self Renewal Octamer Transcription Factor-3 reproductive and urinary physiology Protein Binding |
| Zdroj: | Development (Cambridge, England) article-version (VoR) Version of Record Development (Cambridge, England), 2021, 148 (17), pp.dev199604. ⟨10.1242/dev.199604⟩ |
| ISSN: | 1477-9129 0950-1991 |
| Popis: | The maintenance of pluripotency in mouse embryonic stem cells (ESCs) is governed by the action of an interconnected network of transcription factors. Among them, only Oct4 and Sox2 have been shown to be strictly required for the self-renewal of ESCs and pluripotency, particularly in culture conditions in which differentiation cues are chemically inhibited. Here, we report that the conjunct activity of two orphan nuclear receptors, Esrrb and Nr5a2, parallels the importance of that of Oct4 and Sox2 in naïve mouse ESCs. By occupying a large common set of regulatory elements, these two factors control the binding of Oct4, Sox2 and Nanog to DNA. Consequently, in their absence the pluripotency network collapses and the transcriptome is substantially deregulated, leading to the differentiation of ESCs. Altogether, this work identifies orphan nuclear receptors, previously thought to be performing supportive functions, as a set of core regulators of naïve pluripotency. Summary: Esrrb and Nr5a2, two orphan nuclear receptors, are identified as essential regulators of pluripotency in mouse embryonic stem cells. |
| Databáze: | OpenAIRE |
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