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

Michael Vanlandewijck, Liqun He, Maarja Andaloussi Mäe, Johanna Andrae, Koji Ando, Francesca Del Gaudio, Khayrun Nahar, Thibaud Lebouvier, Bàrbara Laviña, Leonor Gouveia, Ying Sun, Elisabeth Raschperger, Markus Räsänen, Yvette Zarb, Naoki Mochizuki, Annika Keller, Urban Lendahl and Christer Betsholtz ()
Additional contact information
Michael Vanlandewijck: Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI/AZ ICMC)
Liqun He: 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
Maarja Andaloussi Mäe: Genetics and Pathology, Rudbeck Laboratory, Uppsala University
Johanna Andrae: Genetics and Pathology, Rudbeck Laboratory, Uppsala University
Koji Ando: Genetics and Pathology, Rudbeck Laboratory, Uppsala University
Francesca Del Gaudio: Karolinska Institutet
Khayrun Nahar: Genetics and Pathology, Rudbeck Laboratory, Uppsala University
Thibaud Lebouvier: Genetics and Pathology, Rudbeck Laboratory, Uppsala University
Bàrbara Laviña: Genetics and Pathology, Rudbeck Laboratory, Uppsala University
Leonor Gouveia: Genetics and Pathology, Rudbeck Laboratory, Uppsala University
Ying Sun: Zhongyuan Union Genetic Technology Co., Ltd., No.45
Elisabeth Raschperger: Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI/AZ ICMC)
Markus Räsänen: Wihuri Research Institute and Translational Cancer Biology Program, Biomedicum Helsinki, University of Helsinki
Yvette Zarb: Zürich University Hospital, Zürich University
Naoki Mochizuki: National Cerebral and Cardiovascular Center Research Institute
Annika Keller: Zürich University Hospital, Zürich University
Urban Lendahl: Karolinska Institutet
Christer Betsholtz: Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI/AZ ICMC)

Nature, 2018, vol. 554, issue 7693, 475-480

Abstract: 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.

Date: 2018
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DOI: 10.1038/nature25739

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