Tissue-resident PDGFRa stromal cells modulate both fibrosis and tissue revascularization during wound repair

PDGFRa+ cells are interstitial/perivascular mesenchymal progenitor cells that have been associated with fibro-adipogenic processes. However, their function during tissue homeostasis or in response to revascularization and regeneration stimuli remains to be fully defined. Here, by high-throughput transcriptomic analysis, adoptive transfer and multicolor lineage tracking we showed that PDGFRa+ cells from skeletal muscle cluster as a population that is transcriptionally distinct from other mesenchymal stromal cells and with an essential role in tissue revascularization and restructuring of ischemic areas. We further showed that tissue regeneration involves the removal of differentiated PDGFRa+-derived cells, while pathological healing occurred if PDGFRa+-derived cells persisted as terminally differentiated mesenchymal cells (e.g. myofibroblasts). From the perspective of tissue regeneration, these studies support a context-dependent 'yin-yang' biology of PDGFRa+ cells, that possess an innate ability to stabilize newly formed blood vessels and concurrently limit injury expansion after ischemia, while also being capable of promoting fibrosis in an unfavorable environment. Overall design: RNA-seq on mouse tissues