Identification and characterization of PDGFRα+ mesenchymal progenitors in human skeletal muscle

Fatty and fibrous connective tissue formation is a hallmark of diseased skeletal muscle and deteriorates muscle function. We previously identified non-myogenic mesenchymal progenitors that contribute to adipogenesis and fibrogenesis in mouse skeletal muscle. In this study, we report the identification and characterization of a human counterpart to these progenitors. By using PDGFR alpha as a specific marker, mesenchymal progenitors can be identified in the interstitium and isolated from human skeletal muscle. PDGFR alpha(+) cells represent a cell population distinct from CD56(+) myogenic cells, and adipogenic and fibrogenic potentials were highly enriched in the PDGFR alpha(+) population. Activation of PDGFR alpha stimulates proliferation of PDGFR alpha(+) cells through PI3K-Akt and MEK2-MAPK signaling pathways, and aberrant accumulation of PDGFR alpha(+) cells was conspicuous in muscles of patients with both genetic and non-genetic muscle diseases. Our results revealed the pathological relevance of PDGFR alpha(+) mesenchymal progenitors to human muscle diseases and provide a basis for developing therapeutic strategy to treat muscle diseases.