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

• Published in: Cell stem cell 2017-01, Vol.20 (1), p.56-69
• Main Authors: Fry, Christopher S., Kirby, Tyler J., Kosmac, Kate, McCarthy, John J., Peterson, Charlotte A.
• Format: Article
• Language: English
• Subjects: Animals; Carrier Proteins - metabolism; Cell Differentiation - drug effects; Cell Differentiation - genetics; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Cell Survival - drug effects; Cell Survival - genetics; collagen; Collagen - genetics; Collagen - metabolism; Down-Regulation - drug effects; Down-Regulation - genetics; exosomes; Exosomes - drug effects; Exosomes - metabolism; extracellular matrix; Extracellular Matrix - drug effects; Extracellular Matrix - genetics; Extracellular Matrix - metabolism; Fibroblasts - drug effects; Fibroblasts - metabolism; Fibroblasts - pathology; fibrosis; Gene Deletion; Gene Knockdown Techniques; Hypertrophy; Mice; microRNA; MicroRNAs - genetics; MicroRNAs - metabolism; Models, Biological; muscle; Muscle Development - drug effects; Muscle Development - genetics; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - metabolism; Muscle Fibers, Skeletal - pathology; muscle progenitor cells; Muscle, Skeletal - pathology; NIH 3T3 Cells; Pax7; PAX7 Transcription Factor - metabolism; Ribonuclease III - metabolism; satellite cells; Satellite Cells, Skeletal Muscle - drug effects; Satellite Cells, Skeletal Muscle - metabolism; Stem Cells - drug effects; Stem Cells - metabolism; Tamoxifen - pharmacology
• ISSN: 1934-5909; 1875-9777
• DOI: 10.1016/j.stem.2016.09.010

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. [Display omitted] •Myogenic progenitor cells (MPCs) regulate the muscle extracellular matrix•MPCs regulate skeletal muscle fiber hypertrophy independent of fusion•miR-206 in MPC exosomes regulates fibrogenic cell Rrbp1 and collagen expression•MPCs regulate ECM remodeling within 1 week to facilitate fiber growth Stem cells interact with the surrounding extracellular environment to facilitate tissue plasticity. Fry and colleagues report that skeletal muscle myogenic progenitor cells (MPCs) secrete exosomes containing miR-206, which regulates fibrogenic cell collagen expression through repression of Rrbp1. MPC-mediated regulation of the muscle extracellular environment is necessary during early myofiber growth.