Satellite Cell Depletion Disrupts Transcriptional Coordination and Muscle Adaptation to Exercise

Davis A. Englund, Vandre C. Figueiredo, Cory M. Dungan, Kevin A. Murach, Bailey D. Peck, Jennifer M. Petrosino, Camille R. Brightwell, Alec M. Dupont, Ally C. Neal, Christopher S. Fry, Federica Accornero, John J. Mccarthy, Charlotte A. Peterson

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Satellite cells are required for postnatal development, skeletal muscle regeneration across the lifespan, and skeletal muscle hypertrophy prior to maturity. Our group has aimed to address whether satellite cells are required for hypertrophic growth in mature skeletal muscle. Here, we generated a comprehensive characterization and transcriptome-wide profiling of skeletal muscle during adaptation to exercise in the presence or absence of satellite cells in order to identify distinct phenotypes and gene networks influenced by satellite cell content. We administered vehicle or tamoxifen to adult Pax7-DTA mice and subjected them to progressive weighted wheel running (PoWeR). We then performed immunohistochemical analysis and whole-muscle RNA-seq of vehicle (SC+) and tamoxifen-treated (SC-) mice. Further, we performed single myonuclear RNA-seq to provide detailed information on how satellite cell fusion affects myonuclear transcription. We show that while skeletal muscle can mount a robust hypertrophic response to PoWeR in the absence of satellite cells, growth, and adaptation are ultimately blunted. Transcriptional profiling reveals several gene networks key to muscle adaptation are altered in the absence of satellite cells.

Original languageEnglish
Article numberzqaa033
JournalFunction
Volume2
Issue number1
DOIs
StatePublished - 2021

Bibliographical note

Publisher Copyright:
© 2020 The Author(s). Published by Oxford University Press on behalf of American Physiological Society.

Keywords

  • Pax7
  • adaptation
  • exercise
  • hypertrophy
  • muscle function
  • muscle stem cell
  • satellite cell

ASJC Scopus subject areas

  • Molecular Medicine
  • Physiology
  • Cancer Research
  • Cell Biology

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