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

被引：186

作者：

Winkler, Ethan A. ^{[1
,2
,3
,4
]}

Kim, Chang N. ^{[2
,3
,5
,6
]}

Ross, Jayden M. ^{[1
,2
,3
,5
,6
]}

Garcia, Joseph H. ^{[1
]}

Gil, Eugene ^{[1
,2
]}

Oh, Irene ^{[7
]}

Chen, Lindsay Q. ^{[7
]}

Wu, David ^{[1
,2
]}

Catapano, Joshua S. ^{[4
]}

Raygor, Kunal ^{[1
]}

Narsinh, Kazim ^{[8
]}

Kim, Helen ^{[9
]}

Weinsheimer, Shantel ^{[9
]}

Cooke, Daniel L. ^{[3
,8
]}

Walcott, Brian P. ^{[10
]}

Lawton, Michael T. ^{[4
]}

Gupta, Nalin ^{[1
]}

Zlokovic, Berislav, V ^{[11
,12
]}

Chang, Edward F. ^{[1
,3
]}

Abla, Adib A. ^{[1
,3
]}

Lim, Daniel A. ^{[1
,2
,3
,13
]}

Nowakowski, Tomasz J. ^{[1
,2
,3
,5
,6
,14
]}

机构：

[1] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Eli & Edythe Broad Ctr Regenerat Med & Stem Cell, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Weill Inst Neurosci, San Francisco, CA 94143 USA

[4] Barrow Neurol Inst, Dept Neurosurg, Phoenix, AZ USA

[5] Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA

[6] Univ Calif San Francisco, Dept Psychiat & Behav Sci, San Francisco, CA 94143 USA

[7] Rebus Biosyst, Santa Clara, CA USA

[8] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA USA

[9] Univ Calif San Francisco, Ctr Cerebrovasc Res, Dept Anesthesia & Perioperat Care, San Francisco, CA USA

[10] NorthShore Univ HealthSyst, Dept Neurosurg, Evanston, IL USA

[11] Univ Southern Calif, Keck Sch Med, Dept Physiol & Neurosci, Los Angeles, CA USA

[12] Univ Southern Calif, Keck Sch Med, Zilkha Neurogenet Inst, Los Angeles, CA USA

[13] San Francisco VA Med Ctr, San Francisco, CA 94121 USA

[14] Chan Zuckerberg Biohub, San Francisco, CA 94158 USA

来源：

SCIENCE | 2022年 / 375卷 / 6584期

关键词：

SMOOTH-MUSCLE-CELLS; ARTERIOVENOUS-MALFORMATION; RETINOIC ACID; EXPRESSION; PERICYTES; BARRIER; IDENTIFICATION; DIVERSITY; INTEGRITY; PATHWAYS;

D O I：

10.1126/science.abi7377

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：992 / +

页数：39

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