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NANOG initiates epiblast fate through the coordination of pluripotency genes expression

Nicolas Allègre, Sabine Chauveau, Cynthia Dennis, Yoan Renaud, Dimitri Meistermann, Lorena Valverde Estrella, Pierre Pouchin, Michel Cohen-Tannoudji, Laurent David and Claire Chazaud ()
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Nicolas Allègre: Université Clermont Auvergne, CNRS, INSERM, GReD Institute, Faculté de Médecine
Sabine Chauveau: Université Clermont Auvergne, CNRS, INSERM, GReD Institute, Faculté de Médecine
Cynthia Dennis: Université Clermont Auvergne, CNRS, INSERM, GReD Institute, Faculté de Médecine
Yoan Renaud: Université Clermont Auvergne, CNRS, INSERM, GReD Institute, Faculté de Médecine
Dimitri Meistermann: Université de Nantes, CHU Nantes, INSERM
Lorena Valverde Estrella: Université Clermont Auvergne, CNRS, INSERM, GReD Institute, Faculté de Médecine
Pierre Pouchin: Université Clermont Auvergne, CNRS, INSERM, GReD Institute, Faculté de Médecine
Michel Cohen-Tannoudji: Université Paris Cité, CNRS UMR3738, Epigenomics, Proliferation, and the Identity of Cells, Department of Developmental and Stem Cell Biology
Laurent David: Université de Nantes, CHU Nantes, INSERM
Claire Chazaud: Université Clermont Auvergne, CNRS, INSERM, GReD Institute, Faculté de Médecine

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract The epiblast is the source of all mammalian embryonic tissues and of pluripotent embryonic stem cells. It differentiates alongside the primitive endoderm in a “salt and pepper” pattern from inner cell mass (ICM) progenitors during the preimplantation stages through the activity of NANOG, GATA6 and the FGF pathway. When and how epiblast lineage specification is initiated is still unclear. Here, we show that the coordinated expression of pluripotency markers defines epiblast identity. Conversely, ICM progenitor cells display random cell-to-cell variability in expression of various pluripotency markers, remarkably dissimilar from the epiblast signature and independently from NANOG, GATA6 and FGF activities. Coordination of pluripotency markers expression fails in Nanog and Gata6 double KO (DKO) embryos. Collectively, our data suggest that NANOG triggers epiblast specification by ensuring the coordinated expression of pluripotency markers in a subset of cells, implying a stochastic mechanism. These features are likely conserved, as suggested by analysis of human embryos.

Date: 2022
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DOI: 10.1038/s41467-022-30858-8

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