Cell Stem Cell
Volume 24, Issue 6, 6 June 2019, Pages 958-973.e9
Journal home page for Cell Stem Cell

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

https://doi.org/10.1016/j.stem.2019.03.019Get rights and content
Under an Elsevier user license
open archive

Highlights

  • PAX3 expression determines MuSC responses to AHR-dependent environmental stress

  • TCDD exposure elicits aberrant survival, activation, and myofiber fusion in Pax3 MuSCs

  • PAX3-dependent G(alert) and detox pathways protect MuSCs from environmental stress

Summary

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.

Keywords

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

Cited by (0)

10

Senior author

11

Lead Contact