PAX3 Confers Functional Heterogeneity in Skeletal Muscle Stem Cell Responses to Environmental Stress.
Adult Stem Cells
/ physiology
Animals
Cell Differentiation
Cell Survival
Cells, Cultured
Environmental Pollution
/ adverse effects
Mechanistic Target of Rapamycin Complex 1
/ genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
PAX3 Transcription Factor
/ genetics
PAX7 Transcription Factor
/ genetics
Polychlorinated Dibenzodioxins
/ adverse effects
Receptors, Aryl Hydrocarbon
/ metabolism
Satellite Cells, Skeletal Muscle
/ physiology
Signal Transduction
AHR
G(alert)
PAX3
TCDD
environmental stress
muscle stem cells
satellite cells
skeletal muscle
Journal
Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472
Informations de publication
Date de publication:
06 06 2019
06 06 2019
Historique:
received:
08
10
2018
revised:
04
02
2019
accepted:
22
03
2019
pubmed:
23
4
2019
medline:
22
7
2020
entrez:
23
4
2019
Statut:
ppublish
Résumé
Muscle satellite cells (MuSCs) are the quiescent muscle stem cells required for adult skeletal muscle repair. The impact of environmental stress such as pollution on MuSC behavior remains unexplored. We evaluated the impact of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure, a ubiquitous and highly toxic pollutant, on MuSCs by combining in vivo mouse molecular genetic models with ex vivo studies. While all MuSCs express the transcription factor PAX7, we show that a subset also express PAX3 and exhibit resistance to environmental stress. Upon systemic TCDD treatment, PAX3-negative MuSCs display impaired survival, atypical activation, and sporadic differentiation through xenobiotic aryl hydrocarbon receptor signaling. We further show that PAX3-positive MuSCs become sensitized to environmental stress when PAX3 function is impaired and that PAX3-mediated induction of mTORC1 is required for protection. Our study, therefore, identifies a functional heterogeneity of MuSCs in response to environmental stress controlled by PAX3.
Identifiants
pubmed: 31006622
pii: S1934-5909(19)30118-3
doi: 10.1016/j.stem.2019.03.019
pmc: PMC6628901
mid: NIHMS1526993
pii:
doi:
Substances chimiques
PAX3 Transcription Factor
0
PAX7 Transcription Factor
0
Pax7 protein, mouse
0
Polychlorinated Dibenzodioxins
0
Receptors, Aryl Hydrocarbon
0
Pax3 protein, mouse
138016-91-8
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
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
958-973.e9Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL060714
Pays : United States
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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