Single cell atlas of the normal and malformed human brain vasculature

作者：E. Winkler, Chang N. Kim, Jayden Ross, Joseph H. Garcia, Eugene Gil, Irene Oh, Lin Chen, David Wu, J. Catapano, K. Raygor, K. Narsinh, Helen Kim, S. Weinsheimer, D. Cooke, B. Walcott, M. Lawton, Nalin Gupta, B. Zlokovic, E. Chang, A. Abla, D. Lim, T. Nowakowski · 发表于：Science · 年份：2022 · DOI：10.1126/science.abi7377 · 被引用次数：274 · 研究领域：Medicine

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. Description Mapping the brain’s blood vessels Cerebrovascular diseases are a leading cause of death and disability, but our understanding of the cellular and molecular constituents of normal and diseased human cerebrovasculature is incomplete. Winkler et al. generated a cellular-resolution atlas of the adult human cerebrovasculature. The authors used spatial transcriptomics to reveal the geographical organization of an unexpectedly diverse array of molecularly defined cell types within the human brain. They then explored the cellula...