Adipose tissue is a source of fibro-adipogenic progenitors for regenerating skeletal muscles

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. Recently, single-cell RNAseq approaches have revealed phenotype and functional heterogeneity in FAPs. 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. In parallel, we show in healthy humans that exercise-induced muscle stress response triggers the migration of human native ASCs. Additionally, we find that released ASCs infiltrate the damaged muscle, via a platelet dependent mechanism and that blocking ASC infiltration impairs muscle regeneration. Collectively, our data reveal that ScAT is an unsuspected physiological reservoir of regenerative cells that support skeletal muscle regeneration.