Molecular Competition in G1 Controls When Cells Simultaneously Commit to Terminally Differentiate and Exit the Cell Cycle.
G1 lengthening
PPARG
adipocyte
adipogenesis
bistable switch
cell cycle exit
post-mitotic
terminal cell differentiation
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
16 06 2020
16 06 2020
Historique:
received:
22
07
2019
revised:
05
03
2020
accepted:
22
05
2020
entrez:
20
6
2020
pubmed:
20
6
2020
medline:
4
6
2021
Statut:
ppublish
Résumé
Terminal differentiation is essential for the development and maintenance of tissues in all multi-cellular organisms and is associated with permanent exit from the cell cycle. Failure to permanently exit the cell cycle can result in cancer and disease. However, the molecular mechanisms and timing that coordinate differentiation commitment and cell cycle exit are not yet understood. Using live, single-cell imaging of cell cycle progression and differentiation commitment during adipogenesis, we show that a rapid switch mechanism engages exclusively in G1 to trigger differentiation commitment simultaneously with permanent exit from the cell cycle. We identify a molecular competition in G1 between when the differentiation switch is triggered and when the proliferative window closes that allows mitogen and differentiation stimuli to control the balance between terminally differentiating cells produced and progenitor cells kept in reserve, a parameter of critical importance for enabling proper development of tissue domains and organs.
Identifiants
pubmed: 32553172
pii: S2211-1247(20)30749-X
doi: 10.1016/j.celrep.2020.107769
pmc: PMC8198760
mid: NIHMS1604809
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107769Subventions
Organisme : NIDDK NIH HHS
ID : F31 DK112570
Pays : United States
Organisme : NIGMS NIH HHS
ID : P50 GM107615
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK106241
Pays : United States
Organisme : NHGRI NIH HHS
ID : T32 HG000044
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK101743
Pays : United States
Organisme : NIDDK NIH HHS
ID : F32 DK114981
Pays : United States
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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