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

Abstract

Functional revascularization is key to stroke recovery and requires remodeling and regeneration of blood vessels around which is located the brain’s only stromal compartment. Stromal progenitor cells (SPCs) are critical for tissue regeneration following injury in many organs, yet their identity in the brain remains elusive. Here we show that the perivascular niche of brain SPCs includes pericytes, venular smooth muscle cells and perivascular fibroblasts that together help cerebral microvasculature regenerate following experimental stroke. 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 uncovered a transient functional and transcriptional phenotype of stroke-activated pericytes and perivascular fibroblasts. Both populations of these cells remained segregated, displaying distinct angiogenic and fibrogenic profiles. Therefore, pericytes and perivascular fibroblasts are distinct subpopulations of SPCs in the adult brain that coordinate revascularization and scar formation after injury. mehr

Mehr zum Titel

Titel	Brain pericytes and perivascular fibroblasts are stromal progenitors with dual functions in cerebrovascular regeneration after stroke
Medien	Nature Neuroscience
Heft	3
Band	28
ISSN	1546-1726
Verfasser	Louis-Philippe Bernier, Jasmin Hefendehl, R Scott, Lin Tung, Coral-Ann Lewis, Hesham Soliman, Prof. Dr. Stefan Simm, Lasse Dissing-Olesen, Jan Hofmann, David Guo, Murphy DeMeglio, Fabio Rossi, T Underhill, Brian MacVicar
Seiten	517–535
Veröffentlichungsdatum	01.03.2025
Zitation	Bernier, Louis-Philippe; Hefendehl, Jasmin; Scott, R; Tung, Lin; Lewis, Coral-Ann; Soliman, Hesham; Simm, Stefan; Dissing-Olesen, Lasse; Hofmann, Jan; Guo, David; DeMeglio, Murphy; Rossi, Fabio; Underhill, T; MacVicar, Brian (2025): Brain pericytes and perivascular fibroblasts are stromal progenitors with dual functions in cerebrovascular regeneration after stroke. Nature Neuroscience 28 (3), 517–535. DOI: 10.1038/s41593-025-01872-y