TY - JOUR
T1 - Myogenic Progenitor Cells Control Extracellular Matrix Production by Fibroblasts during Skeletal Muscle Hypertrophy
AU - Fry, Christopher S
AU - Kirby, Tyler J
AU - Kosmac, Kate
AU - McCarthy, John J
AU - Peterson, Charlotte A
N1 - * - contributed equally
PY - 2017/1/5
Y1 - 2017/1/5
N2 - 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.
AB - 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.
KW - Animals
KW - Carrier Proteins/metabolism
KW - Cell Differentiation/drug effects
KW - Cell Nucleus/drug effects
KW - Cell Survival/drug effects
KW - Collagen/genetics
KW - Down-Regulation/drug effects
KW - Exosomes/drug effects
KW - Extracellular Matrix/drug effects
KW - Fibroblasts/drug effects
KW - Gene Deletion
KW - Gene Knockdown Techniques
KW - Hypertrophy
KW - Mice
KW - MicroRNAs/genetics
KW - Models, Biological
KW - Muscle Development/drug effects
KW - Muscle Fibers, Skeletal/drug effects
KW - Muscle, Skeletal/pathology
KW - NIH 3T3 Cells
KW - PAX7 Transcription Factor/metabolism
KW - Ribonuclease III/metabolism
KW - Satellite Cells, Skeletal Muscle/drug effects
KW - Stem Cells/drug effects
KW - Tamoxifen/pharmacology
U2 - 10.1016/j.stem.2016.09.010
DO - 10.1016/j.stem.2016.09.010
M3 - Article
C2 - 27840022
VL - 20
SP - 56
EP - 69
JO - Cell Stem Cell
JF - Cell Stem Cell
SN - 1934-5909
IS - 1
ER -