In vitro capture and characterization of embryonic rosette-stage pluripotency between naive and primed states.

Animals Blastocyst / metabolism Cell Differentiation / physiology Chromatin / metabolism Embryonic Stem Cells / metabolism Female Gene Expression Regulation, Developmental / physiology Germ Layers / metabolism Male Mice Mice, Inbred C57BL Morphogenesis / physiology Otx Transcription Factors / metabolism Pluripotent Stem Cells / metabolism

Journal

Nature cell biology

ISSN: 1476-4679

Titre abrégé: Nat Cell Biol

Pays: England

ID NLM: 100890575

Informations de publication

Date de publication:
05 2020

Historique:

received: 25 10 2018

accepted: 20 03 2020

pubmed: 6 5 2020

medline: 8 7 2020

entrez: 6 5 2020

Statut: ppublish

Résumé

Following implantation, the naive pluripotent epiblast of the mouse blastocyst generates a rosette, undergoes lumenogenesis and forms the primed pluripotent egg cylinder, which is able to generate the embryonic tissues. How pluripotency progression and morphogenesis are linked and whether intermediate pluripotent states exist remain controversial. We identify here a rosette pluripotent state defined by the co-expression of naive factors with the transcription factor OTX2. Downregulation of blastocyst WNT signals drives the transition into rosette pluripotency by inducing OTX2. The rosette then activates MEK signals that induce lumenogenesis and drive progression to primed pluripotency. Consequently, combined WNT and MEK inhibition supports rosette-like stem cells, a self-renewing naive-primed intermediate. Rosette-like stem cells erase constitutive heterochromatin marks and display a primed chromatin landscape, with bivalently marked primed pluripotency genes. Nonetheless, WNT induces reversion to naive pluripotency. The rosette is therefore a reversible pluripotent intermediate whereby control over both pluripotency progression and morphogenesis pivots from WNT to MEK signals.

Identifiants

DOI: 10.1038/s41556-020-0508-x PMID: 32367046

pubmed: 32367046

doi: 10.1038/s41556-020-0508-x

pii: 10.1038/s41556-020-0508-x

doi:

Substances chimiques

Chromatin 0

Otx Transcription Factors 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

534-545

Commentaires et corrections

Type : CommentIn

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