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PAX3 Confers Functional Heterogeneity in Skeletal Muscle Stem Cell Responses to Environmental Stress. | LitMetric

PAX3 Confers Functional Heterogeneity in Skeletal Muscle Stem Cell Responses to Environmental Stress.

Cell Stem Cell

Inserm, IMRB U955-E10, 94000 Créteil, France; Faculté de Médecine, Université Paris Est Créteil, 94000 Créteil, France; Ecole Nationale Vétérinaire d'Alfort, 94700 Maisons-Alfort, France; Etablissement Francais du Sang, 94017 Créteil, France; APHP, Hopital Henri Mondor, DHU Pepsy & Centre de Référence des Maladies Neuromusculaires GNMH, 94000 Créteil, France. Electronic address:

Published: June 2019

AI Article Synopsis

Article Abstract

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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628901PMC
http://dx.doi.org/10.1016/j.stem.2019.03.019DOI Listing

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