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
Affiliations
Jordi Camps
Laboratory of Translational Cardiomyology, Department of Development and Regeneration, Stem Cell Research Institute, KU Leuven, 3000 Leuven, Belgium; Bayer AG, Research & Development, Pharmaceuticals, 13353 Berlin, Germany
Natacha Breuls
Laboratory of Translational Cardiomyology, Department of Development and Regeneration, Stem Cell Research Institute, KU Leuven, 3000 Leuven, Belgium
Alejandro Sifrim
Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium; Wellcome Genome Campus, Wellcome Sanger Institute, Cambridge CB10 1SA, UK
Nefele Giarratana
Laboratory of Translational Cardiomyology, Department of Development and Regeneration, Stem Cell Research Institute, KU Leuven, 3000 Leuven, Belgium
Marlies Corvelyn
Laboratory of Translational Cardiomyology, Department of Development and Regeneration, Stem Cell Research Institute, KU Leuven, 3000 Leuven, Belgium
Laura Danti
Laboratory of Translational Cardiomyology, Department of Development and Regeneration, Stem Cell Research Institute, KU Leuven, 3000 Leuven, Belgium
Hanne Grosemans
Laboratory of Translational Cardiomyology, Department of Development and Regeneration, Stem Cell Research Institute, KU Leuven, 3000 Leuven, Belgium
Sebastiaan Vanuytven
Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium
Irina Thiry
Laboratory for Molecular Virology and Gene Therapy, and Leuven Viral Vector Core, KU Leuven, 3000 Leuven, Belgium
Marzia Belicchi
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, 20122 Milan, Italy
Mirella Meregalli
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, 20122 Milan, Italy
Khrystyna Platko
Department of Medicine, The Research Institute of St. Joe’s Hamilton, Hamilton Centre for Kidney Research, McMaster University, Hamilton, ON L8N 4A6, Canada
Melissa E. MacDonald
Department of Medicine, The Research Institute of St. Joe’s Hamilton, Hamilton Centre for Kidney Research, McMaster University, Hamilton, ON L8N 4A6, Canada
Richard C. Austin
Department of Medicine, The Research Institute of St. Joe’s Hamilton, Hamilton Centre for Kidney Research, McMaster University, Hamilton, ON L8N 4A6, Canada
Rik Gijsbers
Laboratory for Molecular Virology and Gene Therapy, and Leuven Viral Vector Core, KU Leuven, 3000 Leuven, Belgium
Giulio Cossu
Division of Cell Matrix Biology and Regenerative Medicine, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK
Yvan Torrente
Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Centro Dino Ferrari, 20122 Milan, Italy
Thierry Voet
Laboratory of Reproductive Genomics, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium; Wellcome Genome Campus, Wellcome Sanger Institute, Cambridge CB10 1SA, UK
Maurilio Sampaolesi
Laboratory of Translational Cardiomyology, Department of Development and Regeneration, Stem Cell Research Institute, KU Leuven, 3000 Leuven, Belgium; Human Anatomy Unit, Department of Public Health, Experimental and Forensic Medicine, University of Pavia, 27100 Pavia, Italy; Corresponding author
Summary: 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.
