Adipose tissue is a source of regenerative cells that augment the repair of skeletal muscle after injury

Quentin Sastourné-Arrey, Maxime Mathieu, Xavier Contreras, Sylvie Monferran, Virginie Bourlier, Marta Gil-Ortega, Enda Murphy, Claire Laurens, Audrey Varin, Christophe Guissard, Corinne Barreau, Mireille André, Noémie Juin, Marie Marquès, Benoit Chaput, Cédric Moro, Donal O’Gorman, Louis Casteilla, Amandine Girousse and Coralie Sengenès ()
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Quentin Sastourné-Arrey: Université de Toulouse, INSERM, CNRS, EFS, ENVT, Université P. Sabatier
Maxime Mathieu: Université de Toulouse, INSERM, CNRS, EFS, ENVT, Université P. Sabatier
Xavier Contreras: Université de Toulouse, INSERM, CNRS, EFS, ENVT, Université P. Sabatier
Sylvie Monferran: Université de Toulouse, INSERM, CNRS, EFS, ENVT, Université P. Sabatier
Virginie Bourlier: INSERM /Paul Sabatier University UMR 1297, Team MetaDiab
Marta Gil-Ortega: Université de Toulouse, INSERM, CNRS, EFS, ENVT, Université P. Sabatier
Enda Murphy: Dublin City University
Claire Laurens: INSERM /Paul Sabatier University UMR 1297, Team MetaDiab
Audrey Varin: Université de Toulouse, INSERM, CNRS, EFS, ENVT, Université P. Sabatier
Christophe Guissard: Université de Toulouse, INSERM, CNRS, EFS, ENVT, Université P. Sabatier
Corinne Barreau: Université de Toulouse, INSERM, CNRS, EFS, ENVT, Université P. Sabatier
Mireille André: Université de Toulouse, INSERM, CNRS, EFS, ENVT, Université P. Sabatier
Noémie Juin: Université de Toulouse, INSERM, CNRS, EFS, ENVT, Université P. Sabatier
Marie Marquès: INSERM /Paul Sabatier University UMR 1297, Team MetaDiab
Benoit Chaput: Toulouse University Hospital
Cédric Moro: INSERM /Paul Sabatier University UMR 1297, Team MetaDiab
Donal O’Gorman: Dublin City University
Louis Casteilla: Université de Toulouse, INSERM, CNRS, EFS, ENVT, Université P. Sabatier
Amandine Girousse: Université de Toulouse, INSERM, CNRS, EFS, ENVT, Université P. Sabatier
Coralie Sengenès: Université de Toulouse, INSERM, CNRS, EFS, ENVT, Université P. Sabatier

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract Fibro-adipogenic progenitors (FAPs) play a crucial role in skeletal muscle regeneration, as they generate a favorable niche that allows satellite cells to perform efficient muscle regeneration. After muscle injury, FAP content increases rapidly within the injured muscle, the origin of which has been attributed to their proliferation within the muscle itself. However, recent single-cell RNAseq approaches have revealed phenotype and functional heterogeneity in FAPs, raising the question of how this differentiation of regenerative subtypes occurs. Here we report that FAP-like cells residing in subcutaneous adipose tissue (ScAT), the adipose stromal cells (ASCs), are rapidly released from ScAT in response to muscle injury. Additionally, we find that released ASCs infiltrate the damaged muscle, via a platelet-dependent mechanism and thus contribute to the FAP heterogeneity. Moreover, we show that either blocking ASCs infiltration or removing ASCs tissue source impair muscle regeneration. Collectively, our data reveal that ScAT is an unsuspected physiological reservoir of regenerative cells that support skeletal muscle regeneration, underlining a beneficial relationship between muscle and fat.

Date: 2023
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DOI: 10.1038/s41467-022-35524-7

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