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

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2019 Apr 23

PMID 31006622

Citations 45

Authors

Audrey Der Vartanian

Marie Quetin

Stephanie Michineau

Frederic Aurade

Shinichiro Hayashi

Christelle Dubois

Didier Rocancourt

Bernadette Drayton-Libotte

Aniko Szegedi

Margaret Buckingham

Simon J Conway

Marianne Gervais

Frederic Relaix

Affiliations

Soon will be listed here.

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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