Disentangling brain vasculature in neurogenesis and neurodegeneration using single-cell transcriptomics

Single-cell transcriptomics of brain vascular cells reveals distinct subtypes of endothelial and mural cells, as well as transcriptomic profiles defining their organization and zonation in the embryonic and adult brain.Mutual interactions between angiogenesis and neurogenesis promote the formation of the blood–brain barrier and coordinate the proliferation, differentiation, and migration of neural progenitors.A full repertoire of endothelial and mural cell subtypes can be identified in the ventricular and subventricular zones of the cerebral cortex and germinal matrix during embryonic development, as early as the second trimester in humans.Vascularized brain organoids recapitulate many key features of neurovascular coupling during angiogenesis and neurogenesis, including the cell-fate specification of vascular cells, cortical neuron differentiation, and the reduction of cellular stress.Single-cell transcriptomics reveals profound dysfunction in neurovascular and gliovascular coupling as key features in several neurodegenerative diseases. The vasculature is increasingly recognized to impact brain function in health and disease across the life span. During embryonic brain development, angiogenesis and neurogenesis are tightly coupled, coordinating the proliferation, differentiation, and migration of neural and glial progenitors. In the adult brain, neurovascular interactions continue to play essential roles in maintaining brain function and homeostasis. This review focuses on recent advances that leverage single-cell transcriptomics of vascular cells to uncover their subtypes, their organization and zonation in the embryonic and adult brain, and how dysfunction in neurovascular and gliovascular interactions contributes to the pathogenesis of neurodegenerative diseases. Finally, we highlight key challenges for future research in neurovascular biology.