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Nature. 2018 Feb 22;554(7693):475-480. doi: 10.1038/nature25739. Epub 2018 Feb 14.

A molecular atlas of cell types and zonation in the brain vasculature.

Author information

1
Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI/AZ ICMC), Blickagången 6, SE-141 57 Huddinge, Sweden.
2
Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala University, Dag Hammarskjölds väg 20, SE-751 85 Uppsala, Sweden.
3
Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin 300052, China.
4
Department of Cell and Molecular Biology, Karolinska Institutet, Von Eulers väg 3, SE-171 77 Stockholm, Sweden.
5
Inserm U1171, University of Lille, CHU, Memory Center, Distalz, F-59000 Lille, France.
6
Department of Bioinformatics, Zhongyuan Union Genetic Technology Co., Ltd., No.45, the 9th East Road, Tianjin Airport Economic Area, Tianjin 300304, China.
7
Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki, Haartmaninkatu 8, P.O. Box 63, FI-00014 Helsinki, Finland.
8
Division of Neurosurgery, Zürich University Hospital, Zürich University, Zürich, CH-8091, Switzerland.
9
Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Suita, Osaka, Japan.
10
AMED-CREST, National Cerebral and Cardiovascular Center, Suita, Osaka, Japan.

Abstract

Cerebrovascular disease is the third most common cause of death in developed countries, but our understanding of the cells that compose the cerebral vasculature is limited. Here, using vascular single-cell transcriptomics, we provide molecular definitions for the principal types of blood vascular and vessel-associated cells in the adult mouse brain. We uncover the transcriptional basis of the gradual phenotypic change (zonation) along the arteriovenous axis and reveal unexpected cell type differences: a seamless continuum for endothelial cells versus a punctuated continuum for mural cells. We also provide insight into pericyte organotypicity and define a population of perivascular fibroblast-like cells that are present on all vessel types except capillaries. Our work illustrates the power of single-cell transcriptomics to decode the higher organizational principles of a tissue and may provide the initial chapter in a molecular encyclopaedia of the mammalian vasculature.

PMID:
29443965
DOI:
10.1038/nature25739
[Indexed for MEDLINE]

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