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

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  • Michael Vanlandewijck

    (Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI/AZ ICMC)
    Genetics and Pathology, Rudbeck Laboratory, Uppsala University)

  • 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
    Inserm U1171, University of Lille, CHU, Memory Center, Distalz)

  • 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
    AMED-CREST, National Cerebral and Cardiovascular Center)

  • Annika Keller

    (Zürich University Hospital, Zürich University)

  • Urban Lendahl

    (Karolinska Institutet)

  • Christer Betsholtz

    (Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI/AZ ICMC)
    Genetics and Pathology, Rudbeck Laboratory, Uppsala University)

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.

Suggested Citation

  • Michael Vanlandewijck & Liqun He & Maarja Andaloussi Mäe & Johanna Andrae & Koji Ando & Francesca Del Gaudio & Khayrun Nahar & Thibaud Lebouvier & Bàrbara Laviña & Leonor Gouveia & Ying Sun & Elisabet, 2018. "A molecular atlas of cell types and zonation in the brain vasculature," Nature, Nature, vol. 554(7693), pages 475-480, February.
  • Handle: RePEc:nat:nature:v:554:y:2018:i:7693:d:10.1038_nature25739
    DOI: 10.1038/nature25739
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    Cited by:

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    7. Xiaomeng Wan & Jiashun Xiao & Sindy Sing Ting Tam & Mingxuan Cai & Ryohichi Sugimura & Yang Wang & Xiang Wan & Zhixiang Lin & Angela Ruohao Wu & Can Yang, 2023. "Integrating spatial and single-cell transcriptomics data using deep generative models with SpatialScope," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
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    10. Jiyeon Lee & Haeryung Lee & Hyein Lee & Miram Shin & Min-Gi Shin & Jinsoo Seo & Eun Jeong Lee & Sun Ah Park & Soochul Park, 2023. "ANKS1A regulates LDL receptor-related protein 1 (LRP1)-mediated cerebrovascular clearance in brain endothelial cells," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
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    12. Nicholas W. Chavkin & Gael Genet & Mathilde Poulet & Erin D. Jeffery & Corina Marziano & Nafiisha Genet & Hema Vasavada & Elizabeth A. Nelson & Bipul R. Acharya & Anupreet Kour & Jordon Aragon & Steph, 2022. "Endothelial cell cycle state determines propensity for arterial-venous fate," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    13. Laetitia Préau & Anna Lischke & Melanie Merkel & Neslihan Oegel & Maria Weissenbruch & Andria Michael & Hongryeol Park & Dietmar Gradl & Christian Kupatt & Ferdinand Noble, 2024. "Parenchymal cues define Vegfa-driven venous angiogenesis by activating a sprouting competent venous endothelial subtype," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    14. Amy J. Gleichman & Riki Kawaguchi & Michael V. Sofroniew & S. Thomas Carmichael, 2023. "A toolbox of astrocyte-specific, serotype-independent adeno-associated viral vectors using microRNA targeting sequences," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    15. Shujuan Zhao & Kedous Y. Mekbib & Martijn A. Ent & Garrett Allington & Andrew Prendergast & Jocelyn E. Chau & Hannah Smith & John Shohfi & Jack Ocken & Daniel Duran & Charuta G. Furey & Le Thi Hao & P, 2023. "Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    16. Chris Greene & Nicole Hanley & Cristina R. Reschke & Avril Reddy & Maarja A. Mäe & Ruairi Connolly & Claire Behan & Eoin O’Keeffe & Isobel Bolger & Natalie Hudson & Conor Delaney & Michael A. Farrell , 2022. "Microvascular stabilization via blood-brain barrier regulation prevents seizure activity," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    17. Urban Lendahl & Lars Muhl & Christer Betsholtz, 2022. "Identification, discrimination and heterogeneity of fibroblasts," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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