Aging Disrupts Muscle Stem Cell Function by Impairing Matricellular WISP1 Secretion from Fibro-Adipogenic Progenitors.
CCN4
WISP1
aging
fibro-adipogenic progenitors
matricellular signaling
muscle stem cells
regeneration
satellite cell
skeletal muscle
stem cell niche
Journal
Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472
Informations de publication
Date de publication:
07 03 2019
07 03 2019
Historique:
received:
22
12
2016
revised:
15
10
2018
accepted:
17
12
2018
pmc-release:
07
03
2020
pubmed:
29
1
2019
medline:
24
4
2020
entrez:
29
1
2019
Statut:
ppublish
Résumé
Research on age-related regenerative failure of skeletal muscle has extensively focused on the phenotypes of muscle stem cells (MuSCs). In contrast, the impact of aging on regulatory cells in the MuSC niche remains largely unexplored. Here, we demonstrate that aging impairs the function of mouse fibro-adipogenic progenitors (FAPs) and thereby indirectly affects the myogenic potential of MuSCs. Using transcriptomic profiling, we identify WNT1 Inducible Signaling Pathway Protein 1 (WISP1) as a FAP-derived matricellular signal that is lost during aging. WISP1 is required for efficient muscle regeneration and controls the expansion and asymmetric commitment of MuSCs through Akt signaling. Transplantation of young FAPs or systemic treatment with WISP1 restores the myogenic capacity of MuSCs in aged mice and rescues skeletal muscle regeneration. Our work establishes that loss of WISP1 from FAPs contributes to MuSC dysfunction in aged skeletal muscles and demonstrates that this mechanism can be targeted to rejuvenate myogenesis.
Identifiants
pubmed: 30686765
pii: S1934-5909(18)30604-0
doi: 10.1016/j.stem.2018.12.014
pmc: PMC6408230
mid: NIHMS1518846
pii:
doi:
Substances chimiques
CCN Intercellular Signaling Proteins
0
CCN4 protein, human
0
CCN4 protein, mouse
0
Proto-Oncogene Proteins
0
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
433-446.e7Subventions
Organisme : NIAMS NIH HHS
ID : R01 AR044031
Pays : United States
Organisme : CIHR
ID : FDN-148387
Pays : Canada
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2018 Elsevier Inc. All rights reserved.
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