CHD4 ensures stem cell lineage fidelity during skeletal muscle regeneration.
Animals
Cell Differentiation
/ genetics
Cell Lineage
/ genetics
Computational Biology
DNA Helicases
/ genetics
Gene Expression Profiling
Gene Expression Regulation, Developmental
Mi-2 Nucleosome Remodeling and Deacetylase Complex
/ metabolism
Mice
Models, Biological
Muscle, Skeletal
/ physiology
Regeneration
Satellite Cells, Skeletal Muscle
/ cytology
Stem Cells
/ cytology
Chd4
NuRD
lineage maintenance
muscle stem cell
regeneration
satellite cells
skeletal muscle
Journal
Stem cell reports
ISSN: 2213-6711
Titre abrégé: Stem Cell Reports
Pays: United States
ID NLM: 101611300
Informations de publication
Date de publication:
14 09 2021
14 09 2021
Historique:
received:
02
12
2020
revised:
29
07
2021
accepted:
30
07
2021
pubmed:
28
8
2021
medline:
11
3
2022
entrez:
27
8
2021
Statut:
ppublish
Résumé
Regeneration of skeletal muscle requires resident stem cells called satellite cells. Here, we report that the chromatin remodeler CHD4, a member of the nucleosome remodeling and deacetylase (NuRD) repressive complex, is essential for the expansion and regenerative functions of satellite cells. We show that conditional deletion of the Chd4 gene in satellite cells results in failure to regenerate muscle after injury. This defect is principally associated with increased stem cell plasticity and lineage infidelity during the expansion of satellite cells, caused by de-repression of non-muscle-cell lineage genes in the absence of Chd4. Thus, CHD4 ensures that a transcriptional program that safeguards satellite cell identity during muscle regeneration is maintained. Given the therapeutic potential of muscle stem cells in diverse neuromuscular pathologies, CHD4 constitutes an attractive target for satellite cell-based therapies.
Identifiants
pubmed: 34450038
pii: S2213-6711(21)00388-X
doi: 10.1016/j.stemcr.2021.07.022
pmc: PMC8452531
pii:
doi:
Substances chimiques
Mi-2 Nucleosome Remodeling and Deacetylase Complex
EC 3.5.1.98
Mi-2beta protein, mouse
EC 3.6.1.3
DNA Helicases
EC 3.6.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2089-2098Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
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