Transcriptional heterogeneity and cell cycle regulation as central determinants of Primitive Endoderm priming.


Journal

eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614

Informations de publication

Date de publication:
15 08 2022
Historique:
received: 25 03 2022
accepted: 12 08 2022
pubmed: 16 8 2022
medline: 30 8 2022
entrez: 15 8 2022
Statut: epublish

Résumé

During embryonic development cells acquire identity as they proliferate, implying that an intrinsic facet of cell fate choice requires coupling lineage decisions to cell division. How is the cell cycle regulated to promote or suppress heterogeneity and differentiation? We explore this question combining time lapse imaging with single-cell RNA-seq in the contexts of self-renewal, priming, and differentiation of mouse embryonic stem cells (ESCs) towards the Primitive Endoderm (PrE) lineage. Since ESCs are derived from the inner cell mass (ICM) of the mammalian blastocyst, ESCs in standard culture conditions are transcriptionally heterogeneous containing dynamically interconverting subfractions primed for either of the two ICM lineages, Epiblast and PrE. Here, we find that differential regulation of cell cycle can tip the balance between these primed populations, such that naïve ESC culture promotes Epiblast-like expansion and PrE differentiation stimulates the selective survival and proliferation of PrE-primed cells. In endoderm differentiation, this change is accompanied by a counter-intuitive increase in G1 length, also observed

Identifiants

pubmed: 35969041
doi: 10.7554/eLife.78967
pii: 78967
pmc: PMC9417417
doi:
pii:

Substances chimiques

Fibroblast Growth Factors 62031-54-3

Banques de données

GEO
['GSE200534', 'GSE123046']

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2022, Perera et al.

Déclaration de conflit d'intérêts

MP, SN, MP, SP, RM, AT No competing interests declared, JB Reviewing editor, eLife

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Auteurs

Marta Perera (M)

reNEW UCPH - The Novo Nordisk Foundation Center for Stem Cell Medicine, University of Copenhagen, Copenhagen, Denmark.

Silas Boye Nissen (SB)

Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.

Martin Proks (M)

reNEW UCPH - The Novo Nordisk Foundation Center for Stem Cell Medicine, University of Copenhagen, Copenhagen, Denmark.

Sara Pozzi (S)

reNEW UCPH - The Novo Nordisk Foundation Center for Stem Cell Medicine, University of Copenhagen, Copenhagen, Denmark.

Rita S Monteiro (RS)

reNEW UCPH - The Novo Nordisk Foundation Center for Stem Cell Medicine, University of Copenhagen, Copenhagen, Denmark.

Ala Trusina (A)

Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.

Joshua M Brickman (JM)

reNEW UCPH - The Novo Nordisk Foundation Center for Stem Cell Medicine, University of Copenhagen, Copenhagen, Denmark.

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Classifications MeSH