Interstitial Cell Remodeling Promotes Aberrant Adipogenesis in Dystrophic Muscles

Jordi Camps, Natacha Breuls, Alejandro Sifrim, Nefele Giarratana, Marlies Corvelyn, Laura Danti, Hanne Grosemans, Sebastiaan Vanuytven, Irina Thiry, Marzia Belicchi, Mirella Meregalli, Khrystyna Platko, Melissa E. MacDonald, Richard C. Austin, Rik Gijsbers, Giulio Cossu, Yvan Torrente, Thierry Voet, Maurilio Sampaolesi

Research output: Contribution to journalArticlepeer-review

Abstract

Fibrosis and fat replacement in skeletal muscle are major complications that lead to a loss of mobility in chronic muscle disorders, such as muscular dystrophy. However, the in vivo properties of adipogenic stem and precursor cells remain unclear, mainly due to the high cell heterogeneity in skeletal muscles. Here, we use single-cell RNA sequencing to decomplexify interstitial cell populations in healthy and dystrophic skeletal muscles. We identify an interstitial CD142-positive cell population in mice and humans that is responsible for the inhibition of adipogenesis through GDF10 secretion. Furthermore, we show that the interstitial cell composition is completely altered in muscular dystrophy, with a near absence of CD142-positive cells. The identification of these adipo-regulatory cells in the skeletal muscle aids our understanding of the aberrant fat deposition in muscular dystrophy, paving the way for treatments that could counteract degeneration in patients with muscular dystrophy.

Original languageEnglish
Article number107597
JournalCell Reports
Volume31
Issue number5
DOIs
Publication statusPublished - May 5 2020

Keywords

  • adipogenesis
  • GDF10
  • interstitial stromal cells
  • muscular dystrophy
  • single-cell transcriptomics
  • skeletal muscle

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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