A Novel Role of Satellite Cells in Skeletal Muscle Hypertrophy

Satellite cells are skeletal muscle stem cells that are absolutely required for effective muscle regeneration. Satellite cells have also been shown to be involved in muscle hypertrophy by increasing myonuclear abundance as a result of their fusion to the myofiber. Studies investigating the necessity of satellite cell fusion for hypertrophic growth discovered a novel role for satellite cells involving intercellular communication to other mononucleated cells within the muscle. Initial studies revealed satellite cells were communicating with fibroblasts through the delivery miRNAs by exosomes. In particular, the delivery myomiR miR-206 by satellite cell-derived exosomes was shown to repress the expression of Rrbp1, a master regulator collagen synthesis. Through this mechanism, satellite cells were involved in regulating the proper remodeling of the extracellular matrix which was critical for optimal muscle growth. Further studies using single-cell RNA-sequencing demonstrated that satellite cells were also communicating with endothelial cell and fibro-adipogenic progenitor cells during muscle hypertrophy. The emerging picture is one in which satellite cells sit at the center of an intercellular communication network that early on coordinates the activity other cells to provide a cellular environment that permits robust hypertrophic growth of skeletal muscle.