CHARACTERIZATION OF NOVEL SUBPOPULATIONS OF NON-MURAL PDGFRBETA+ CELLS IN NEUROVASCULAR HEALTH AND DISEASE

Brain homeostasis narrowly depends upon the concerted crosstalk among neurons, glial cells, and vascular cells that generates critical neurovascular functions, including the regulation of cerebral blood flow (CBF), blood-brain barrier (BBB) integrity, vascular stability, and immune modulation. Brain cells expressing platelet-derived growth factor receptor (PDGFR)β include essentially mural cells, mainly pericytes, vascular smooth muscle cells (vSMCs), fibroblasts, which act as gatekeepers of immune and vascular functions. The recent evidence is revealing important morphological and molecular heterogeneity within brain PDGFRβ⁺ cells that remains to be fully characterized. Elucidating the diversity of PDGFRβ cells will provide new fundamental insights into neurovascular functions and will pave the way to develop new therapies for various brain diseases. Using multidisciplinary approaches combining genetic tools, viral approaches, transcriptomic studies and imaging techniques, our investigations identified novel subpopulations of bone marrow-derived PDGFRβ⁺ cells that actively infiltrate the injured brain after stroke as well as resident non-mural perivascular PDGFRβ⁺ cells that exhibit a distinct phenotype in comparison to the other mural PDGFRβ⁺ cells in response to brain injury after stroke. Moreover, our findings indicate that the infiltrating bone marrow-derived PDGFRβ⁺ cells acquire specific immune properties and actively shape immune and vascular responses, and that the resident non-mural PDGFRβ⁺ cells represent a novel subtype of glial cells that play a previously undescribed role in maintaining vascular stability and neuronal circuitry. Herein, our results identified and characterized novel subpopulations of PDGFRβ⁺ cells that play distinct roles in regulating immune and vascular responses affecting neuronal functions under physiological and pathological conditions.