Myogenic Progenitor Cells Control Extracellular Matrix Production by Fibroblasts during Skeletal Muscle Hypertrophy

Christopher S Fry*, Tyler J Kirby*, Kate Kosmac, John J McCarthy, Charlotte A Peterson

Research output: Contribution to journalArticleAcademicpeer-review

234 Citations (Scopus)

Abstract

Satellite cells, the predominant stem cell population in adult skeletal muscle, are activated in response to hypertrophic stimuli and give rise to myogenic progenitor cells (MPCs) within the extracellular matrix (ECM) that surrounds myofibers. This ECM is composed largely of collagens secreted by interstitial fibrogenic cells, which influence satellite cell activity and muscle repair during hypertrophy and aging. Here we show that MPCs interact with interstitial fibrogenic cells to ensure proper ECM deposition and optimal muscle remodeling in response to hypertrophic stimuli. MPC-dependent ECM remodeling during the first week of a growth stimulus is sufficient to ensure long-term myofiber hypertrophy. MPCs secrete exosomes containing miR-206, which represses Rrbp1, a master regulator of collagen biosynthesis, in fibrogenic cells to prevent excessive ECM deposition. These findings provide insights into how skeletal stem and progenitor cells interact with other cell types to actively regulate their extracellular environments for tissue maintenance and adaptation.

Original languageEnglish
Pages (from-to)56-69
Number of pages14
JournalCell Stem Cell
Volume20
Issue number1
DOIs
Publication statusPublished - 5 Jan 2017

Keywords

  • Animals
  • Carrier Proteins/metabolism
  • Cell Differentiation/drug effects
  • Cell Nucleus/drug effects
  • Cell Survival/drug effects
  • Collagen/genetics
  • Down-Regulation/drug effects
  • Exosomes/drug effects
  • Extracellular Matrix/drug effects
  • Fibroblasts/drug effects
  • Gene Deletion
  • Gene Knockdown Techniques
  • Hypertrophy
  • Mice
  • MicroRNAs/genetics
  • Models, Biological
  • Muscle Development/drug effects
  • Muscle Fibers, Skeletal/drug effects
  • Muscle, Skeletal/pathology
  • NIH 3T3 Cells
  • PAX7 Transcription Factor/metabolism
  • Ribonuclease III/metabolism
  • Satellite Cells, Skeletal Muscle/drug effects
  • Stem Cells/drug effects
  • Tamoxifen/pharmacology

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