A single-cell atlas of the normal and malformed human brain vasculature

EA Winkler, CN Kim, JM Ross, JH Garcia, E Gil, I Oh… - Science, 2022 - science.org
EA Winkler, CN Kim, JM Ross, JH Garcia, E Gil, I Oh, LQ Chen, D Wu, JS Catapano
Science, 2022science.org
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. We profiled transcriptomes of 181,388 cells
to define a cell atlas of the adult 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 …
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. We profiled transcriptomes of 181,388 cells to define a cell atlas of the adult 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, which are a leading cause of stroke in young people, and identified pathologic endothelial transformations with abnormal vascular patterning and the ontology of vascularly derived inflammation. We illustrate the interplay between vascular and immune cells that contributes to brain hemorrhage and catalog opportunities for targeting angiogenic and inflammatory programs in vascular malformations.
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