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

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. The dynamics of fibroadipogenic progenitors (FAPs) after muscle injury are crucial to ensure efficient regeneration. Here the authors show that a pool of FAPs originates from adipose tissue and are necessary for effective muscle regeneration.

Automated summary

Fibro-adipogenic progenitors (FAPs) are crucial for skeletal muscle regeneration, and recent research has shown that a subset of FAP-like cells released from subcutaneous adipose tissue (ScAT) plays a role in this process. These cells, known as adipose stromal cells (ASCs), infiltrate the injured muscle through a platelet-dependent mechanism and contribute to the heterogeneity of FAPs. Blocking ASCs infiltration or removing ASCs tissue source impairs muscle regeneration, highlighting the importance of ScAT as a physiological reservoir of regenerative cells.