TY - JOUR
T1 - Interstitial Cell Remodeling Promotes Aberrant Adipogenesis in Dystrophic Muscles
AU - Camps, Jordi
AU - Breuls, Natacha
AU - Sifrim, Alejandro
AU - Giarratana, Nefele
AU - Corvelyn, Marlies
AU - Danti, Laura
AU - Grosemans, Hanne
AU - Vanuytven, Sebastiaan
AU - Thiry, Irina
AU - Belicchi, Marzia
AU - Meregalli, Mirella
AU - Platko, Khrystyna
AU - MacDonald, Melissa E.
AU - Austin, Richard C.
AU - Gijsbers, Rik
AU - Cossu, Giulio
AU - Torrente, Yvan
AU - Voet, Thierry
AU - Sampaolesi, Maurilio
PY - 2020/5/5
Y1 - 2020/5/5
N2 - 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.
AB - 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.
KW - adipogenesis
KW - GDF10
KW - interstitial stromal cells
KW - muscular dystrophy
KW - single-cell transcriptomics
KW - skeletal muscle
UR - http://www.scopus.com/inward/record.url?scp=85084159276&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85084159276&partnerID=8YFLogxK
U2 - 10.1016/j.celrep.2020.107597
DO - 10.1016/j.celrep.2020.107597
M3 - Article
AN - SCOPUS:85084159276
VL - 31
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 5
M1 - 107597
ER -