Expansion of ventral foregut is linked to changes in the enhancer landscape for organ-specific differentiation.
Journal
Nature cell biology
ISSN: 1476-4679
Titre abrégé: Nat Cell Biol
Pays: England
ID NLM: 100890575
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
received:
11
02
2022
accepted:
14
12
2022
pubmed:
24
1
2023
medline:
17
3
2023
entrez:
23
1
2023
Statut:
ppublish
Résumé
Cell proliferation is fundamental for almost all stages of development and differentiation that require an increase in cell number. Although cell cycle phase has been associated with differentiation, the actual process of proliferation has not been considered as having a specific role. Here we exploit human embryonic stem cell-derived endodermal progenitors that we find are an in vitro model for the ventral foregut. These cells exhibit expansion-dependent increases in differentiation efficiency to pancreatic progenitors that are linked to organ-specific enhancer priming at the level of chromatin accessibility and the decommissioning of lineage-inappropriate enhancers. Our findings suggest that cell proliferation in embryonic development is about more than tissue expansion; it is required to ensure equilibration of gene regulatory networks allowing cells to become primed for future differentiation. Expansion of lineage-specific intermediates may therefore be an important step in achieving high-fidelity in vitro differentiation.
Identifiants
pubmed: 36690849
doi: 10.1038/s41556-022-01075-8
pii: 10.1038/s41556-022-01075-8
pmc: PMC10014581
mid: EMS158542
doi:
Substances chimiques
Chromatin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
481-492Subventions
Organisme : Medical Research Council
ID : MR/R000638/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S036121/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00007/2
Pays : United Kingdom
Informations de copyright
© 2023. The Author(s).
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