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 journalArticlepeer-review

    251 Scopus citations

    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 (US)
    Pages (from-to)56-69
    Number of pages14
    JournalCell Stem Cell
    Volume20
    Issue number1
    DOIs
    StatePublished - Jan 5 2017

    Keywords

    • Pax7
    • collagen
    • exosomes
    • extracellular matrix
    • fibrosis
    • hypertrophy
    • microRNA
    • muscle
    • muscle progenitor cells
    • satellite cells

    ASJC Scopus subject areas

    • Molecular Medicine
    • Genetics
    • Cell Biology

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