A Single-cell Atlas of the Normal and Malformed Human Brain Vasculature

Overview

Journal Science

Specialty Science

Date 2022 Jan 27

PMID 35084939

Authors

Ethan A Winkler

Chang N Kim

Jayden M Ross

Joseph H Garcia

Eugene Gil

Irene Oh

Lindsay Q Chen

David Wu

Joshua S Catapano

Kunal Raygor

Kazim Narsinh

Helen Kim

Shantel Weinsheimer

Daniel L Cooke

Brian P Walcott

Michael T Lawton

Nalin Gupta

Berislav V Zlokovic

Edward F Chang

Adib A Abla

Daniel A Lim

Tomasz J Nowakowski

Affiliations

Soon will be listed here.

Abstract

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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