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

Audrey Der Vartanian, Marie Quétin, Stéphanie Michineau, Frédéric Auradé, Shinichiro Hayashi, Christelle Dubois, Didier Rocancourt, Bernadette Drayton-Libotte, Anikó Szegedi, Margaret Buckingham, Simon J. Conway, Marianne Gervais, Frédéric Relaix

Research output: Contribution to journalArticle

7 Scopus citations

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. Der Vartanian and colleagues identify a functional heterogeneity of skeletal muscle stem cell response to environmental stress. While PAX3-negative muscle stem cells display impaired survival, aberrant activation, and sporadic fusion to myofibers upon TCDD exposure, PAX3-positive muscle stem cells are protected against the pollutant through an mTORC1-dependent G(alert) response.

Original languageEnglish (US)
Pages (from-to)958-973.e9
JournalCell Stem Cell
Volume24
Issue number6
DOIs
StatePublished - Jun 6 2019

Keywords

  • AHR
  • G(alert)
  • PAX3
  • TCDD
  • environmental stress
  • muscle stem cells
  • satellite cells
  • skeletal muscle

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Cell Biology

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    Der Vartanian, A., Quétin, M., Michineau, S., Auradé, F., Hayashi, S., Dubois, C., Rocancourt, D., Drayton-Libotte, B., Szegedi, A., Buckingham, M., Conway, S. J., Gervais, M., & Relaix, F. (2019). PAX3 Confers Functional Heterogeneity in Skeletal Muscle Stem Cell Responses to Environmental Stress. Cell Stem Cell, 24(6), 958-973.e9. https://doi.org/10.1016/j.stem.2019.03.019