Single cell atlas of the normal and malformed human brain vasculature

Cerebrovascular diseases are a leading cause of death and neurologic disability. Further understanding of disease mechanisms and therapeutic strategies requires a deeper knowledge of cerebrovascular cells in humans. Here, we profiled transcriptomes of 181,388 single-cells from the adult cerebrovasculature. Our results define a cell atlas of the human cerebrovasculature, including endothelial cell molecular signatures with arteriovenous segmentation and expanded perivascular cell diversity. By leveraging this reference, we investigated cellular and molecular perturbations in brain arteriovenous malformations, a leading cause of stroke in young people, and identified pathologic endothelial transformations with abnormal vascular patterning and the ontology of vascular-derived inflammation. Herein, we illustrated an interplay between vascular and immune cells contributory to brain hemorrhage and cataloged opportunities for targeting angiogenic and inflammatory programs in vascular malformations.