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Publication : The combined action of Esrrb and Nr5a2 is essential for murine naïve pluripotency.

First Author  Festuccia N Year  2021
Journal  Development Volume  148
Issue  17 PubMed ID  34397088
Mgi Jnum  J:359789 Mgi Id  MGI:6761829
Doi  10.1242/dev.199604 Citation  Festuccia N, et al. (2021) The combined action of Esrrb and Nr5a2 is essential for murine naive pluripotency. Development 148(17)
abstractText  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 naive 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 naive pluripotency.
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