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

doi:10.1016/j.celrep.2020.107597

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

Fondazione IRCCS Ca' Granda- Ospedale Maggiore Policlinico

Research output: Contribution to journal › Article › peer-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 language	English
Article number	107597
Journal	Cell Reports
Volume	31
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2020.107597
Publication status	Published - 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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10.1016/j.celrep.2020.107597

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Camps, J., Breuls, N., Sifrim, A., Giarratana, N., Corvelyn, M., Danti, L., Grosemans, H., Vanuytven, S., Thiry, I., Belicchi, M., Meregalli, M., Platko, K., MacDonald, M. E., Austin, R. C., Gijsbers, R., Cossu, G., Torrente, Y., Voet, T., & Sampaolesi, M. (2020). Interstitial Cell Remodeling Promotes Aberrant Adipogenesis in Dystrophic Muscles. Cell Reports, 31(5), [107597]. https://doi.org/10.1016/j.celrep.2020.107597

Interstitial Cell Remodeling Promotes Aberrant Adipogenesis in Dystrophic Muscles. / Camps, Jordi; Breuls, Natacha; Sifrim, Alejandro; Giarratana, Nefele; Corvelyn, Marlies; Danti, Laura; Grosemans, Hanne; Vanuytven, Sebastiaan; Thiry, Irina; Belicchi, Marzia; Meregalli, Mirella; Platko, Khrystyna; MacDonald, Melissa E.; Austin, Richard C.; Gijsbers, Rik; Cossu, Giulio; Torrente, Yvan; Voet, Thierry; Sampaolesi, Maurilio.

In: Cell Reports, Vol. 31, No. 5, 107597, 05.05.2020.

Research output: Contribution to journal › Article › peer-review

Camps, J, Breuls, N, Sifrim, A, Giarratana, N, Corvelyn, M, Danti, L, Grosemans, H, Vanuytven, S, Thiry, I, Belicchi, M, Meregalli, M, Platko, K, MacDonald, ME, Austin, RC, Gijsbers, R, Cossu, G, Torrente, Y, Voet, T & Sampaolesi, M 2020, 'Interstitial Cell Remodeling Promotes Aberrant Adipogenesis in Dystrophic Muscles', Cell Reports, vol. 31, no. 5, 107597. https://doi.org/10.1016/j.celrep.2020.107597

Camps, Jordi ; Breuls, Natacha ; Sifrim, Alejandro ; Giarratana, Nefele ; Corvelyn, Marlies ; Danti, Laura ; Grosemans, Hanne ; Vanuytven, Sebastiaan ; Thiry, Irina ; Belicchi, Marzia ; Meregalli, Mirella ; Platko, Khrystyna ; MacDonald, Melissa E. ; Austin, Richard C. ; Gijsbers, Rik ; Cossu, Giulio ; Torrente, Yvan ; Voet, Thierry ; Sampaolesi, Maurilio. / Interstitial Cell Remodeling Promotes Aberrant Adipogenesis in Dystrophic Muscles. In: Cell Reports. 2020 ; Vol. 31, No. 5.

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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.",

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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

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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.

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KW - GDF10

KW - interstitial stromal cells

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Interstitial Cell Remodeling Promotes Aberrant Adipogenesis in Dystrophic Muscles

Abstract

Keywords

ASJC Scopus subject areas

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