Brain pericytes and perivascular fibroblasts are stromal progenitors that coordinate cerebrovascular regeneration after stroke

Functional revascularization is key to stroke recovery and requires remodeling of the vascular wall, the brains only stromal compartment. Stromal progenitor cells (SPC) are 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 pericytes and perivascular fibroblasts form a perivascular niche of brain SPCs that 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 SPC populations remain segregated, displaying angiogenic and fibrogenic profiles, respectively. In the adult brain, pericytes and perivascular fibroblasts are therefore distinct subpopulations of stromal progenitors that coordinate revascularization and scar formation after injury.