Crosstalk between macrophages and fibro-adipogenic progenitors during muscle regeneration

The purpose of this study is to investigate how immune cells (macrophages) are closely linked with fibro-adipogenic progenitors (FAPs) during recovery processe. We report that the depletion of Mrc1+ (gene encoding CD206) M2-like macrophages promoted the recovery of muscle after injury. A total RNA sequence analysis of whole muscle or isolated FAPs revealed that the depletion of Mrc1+ M2-like macrophages resulted in the activation of FAPs. Activated FAPs secrete follistatin (Fst), a promyogenic factor, boosting the recovery process. We further determined that the knockdown of FAPs-derived Fst delayed the recovery process. Mechanistically, Mrc1+ M2-like macrophages-specific TGF-b1 inhibited the activation of FAPs, and the FAPs failed to secrete Fst. Overall design: mRNA profiles of whole muscle 4,7,14 post-day injury (cardiotoxin [CTX]-induced muscle injury) and mRNA profile of isolated FAPs from 7 post-day injured muscle of wild type (WT) and CD206DTR mice were generated by deep sequencing.