The role of oligodendrocyte progenitor cells in the spatiotemporal vascularization of the human and mouse neocortex

Abstract Brain vasculature formation begins with vessel invasion from the perineural vascular plexus, which expands through vessel sprouting and growth. Recent studies have indicated the existence of oligodendrocyte‐vascular crosstalk during development. However, the relationship between oligodendrocyte progenitor cells (OPCs) and the ordered spatiotemporal vascularization of the neocortex has not been elucidated. Our findings suggest that OPCs play a complex role in the vessel density of the embryonic and postnatal neocortex. Analyses of normal human and mouse embryonic cerebral cortex show that vascularization and OPC distribution are tightly controlled in a spatially and temporally restricted manner, exhibiting a positive correlation. Loss of OPCs at both embryonic and postnatal stages led to a reduction in vascular density, suggesting that OPC populations play a role in vascular density. Nonetheless, dynamic observation on cultured brain slices and staining of tissue sections indicate that OPC migration is unassociated with the proximity to blood vessels, primarily occurring along radial glial cell processes. Additionally, in vitro experiments demonstrate that OPC secretions promote vascular endothelial cell (VEC) growth. Together, these observations suggest that vessel density is influenced by OPC secretions.