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

A. Uezumi, S. Fukada, N. Yamamoto, M. Ikemoto-Uezumi, M. Nakatani, M. Morita, A. Yamaguchi, H. Yamada, I. Nishino, Y. Hamada, K. Tsuchida

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Abstract

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 as a specific marker, mesenchymal progenitors can be identified in the interstitium and isolated from human skeletal muscle. PDGFR + cells represent a cell population distinct from CD56 + myogenic cells, and adipogenic and fibrogenic potentials were highly enriched in the PDGFR + population. Activation of PDGFR stimulates proliferation of PDGFR + cells through PI3K-Akt and MEK2-MAPK signaling pathways, and aberrant accumulation of PDGFR + cells was conspicuous in muscles of patients with both genetic and non-genetic muscle diseases. Our results revealed the pathological relevance of PDGFR + mesenchymal progenitors to human muscle diseases and provide a basis for developing therapeutic strategy to treat muscle diseases.

Original languageEnglish
Article numbere1186
JournalCell Death and Disease
Volume5
Issue number4
DOIs
Publication statusPublished - 04-2014

All Science Journal Classification (ASJC) codes

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

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    Uezumi, A., Fukada, S., Yamamoto, N., Ikemoto-Uezumi, M., Nakatani, M., Morita, M., Yamaguchi, A., Yamada, H., Nishino, I., Hamada, Y., & Tsuchida, K. (2014). Identification and characterization of PDGFR + mesenchymal progenitors in human skeletal muscle. Cell Death and Disease, 5(4), [e1186]. https://doi.org/10.1038/cddis.2014.161