Brain pericytes and perivascular fibroblasts are stromal progenitors with dual functions in cerebrovascular regeneration after stroke

Functional revascularization is key to stroke recovery and requires remodelling of blood vessels, around which is located the brain’s only stromal compartment. Stromal progenitor cells (SPC) form a functional grouping of cells critical for tissue regeneration following injury in many organs, yet their identity in the brain remains elusive despite implications in neovascularization and scar formation. Here we show that the perivascular niche of brain SPCs includes pericytes, venular smooth muscle cells and a distinct population of perivascular fibroblasts, that together help regenerate the cerebral microvasculature following stroke. The ischemic injury triggers amplification of pericytes and perivascular fibroblasts in the infarct region where they associate with endothelial cells inside a reactive astrocyte border. Fate-tracking of Hic1+ SPCs uncovers a transient functional and transcriptional phenotype of stroke-activated pericytes and perivascular fibroblasts, where both populations remain segregated, displaying dichotomous angiogenic and fibrogenic profiles. In the adult brain, pericytes and perivascular fibroblasts are therefore distinct subpopulations of stromal progenitors that coordinate revascularization and scar formation after injury.