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

Authors

Ethan A. Winkler, Department of Neurological Surgery, University of California, San Francisco, CA, USA.
Chang N. Kim, Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, USA.
Jayden M. Ross, Department of Neurological Surgery, University of California, San Francisco, CA, USA.
Joseph H. Garcia, Department of Neurological Surgery, University of California, San Francisco, CA, USA.
Eugene Gil, Department of Neurological Surgery, University of California, San Francisco, CA, USA.
Irene Oh, Rebus Biosystems, Santa Clara, CA, USA.
Lindsay Q. Chen, Rebus Biosystems, Santa Clara, CA, USA.
David Wu, Department of Neurological Surgery, University of California, San Francisco, CA, USA.
Joshua S. Catapano, Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, USA.Follow
Kunal Raygor, Department of Neurological Surgery, University of California, San Francisco, CA, USA.
Kazim Narsinh, Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA, USA.
Helen Kim, Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, USA.
Shantel Weinsheimer, Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA, USA.
Daniel L. Cooke, Weill Institute for Neurosciences, University of California, San Francisco, CA, USA.
Brian P. Walcott, Department of Neurosurgery, NorthShore University HealthSystem, Evanston, IL, USA.
Michael T. Lawton, Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ, USA.Follow
Nalin Gupta, Department of Neurological Surgery, University of California, San Francisco, CA, USA.
Berislav V. Zlokovic, Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Edward F. Chang, Department of Neurological Surgery, University of California, San Francisco, CA, USA.
Adib A. Abla, Department of Neurological Surgery, University of California, San Francisco, CA, USA.
Daniel A. Lim, Department of Neurological Surgery, University of California, San Francisco, CA, USA.
Tomasz J. Nowakowski, Department of Neurological Surgery, University of California, San Francisco, CA, USA.

Document Type

Article

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.

Medical Subject Headings

Adult; Blood Vessels (cytology, pathology, physiology, physiopathology); Brain (blood supply); Cells, Cultured; Cerebral Cortex (blood supply); Cerebral Hemorrhage (pathology, physiopathology); Cerebrovascular Circulation; Endothelial Cells (cytology, pathology, physiology); Fibroblasts (cytology, physiology); Humans; Inflammation; Intracranial Arteriovenous Malformations (metabolism, pathology); Monocytes (cytology, physiology); Muscle, Smooth, Vascular (cytology, pathology, physiology); Pericytes (cytology, physiology); RNA-Seq; Single-Cell Analysis; Transcriptome

Publication Date

3-4-2022

Publication Title

Science (New York, N.Y.)

E-ISSN

1095-9203

Volume

375

Issue

6584

First Page

eabi7377

PubMed ID

35084939

Digital Object Identifier (DOI)

10.1126/science.abi7377

Recommended Citation

Winkler, Ethan A.; Kim, Chang N.; Ross, Jayden M.; Garcia, Joseph H.; Gil, Eugene; Oh, Irene; Chen, Lindsay Q.; Wu, David; Catapano, Joshua S.; Raygor, Kunal; Narsinh, Kazim; Kim, Helen; Weinsheimer, Shantel; Cooke, Daniel L.; Walcott, Brian P.; Lawton, Michael T.; Gupta, Nalin; Zlokovic, Berislav V.; Chang, Edward F.; Abla, Adib A.; Lim, Daniel A.; and Nowakowski, Tomasz J., "A single-cell atlas of the normal and malformed human brain vasculature" (2022). Neurosurgery. 1554.
https://scholar.barrowneuro.org/neurosurgery/1554