Single cell transcriptomics reveals functionally specialized vascular endothelium in brain

  1. Hyun-Woo Jeong  Is a corresponding author
  2. Rodrigo Diéguez-Hurtado
  3. Hendrik Arf
  4. Jian Song
  5. Hongryeol Park
  6. Kai Kruse
  7. Lydia Sorokin
  8. Ralf H Adams  Is a corresponding author
  1. Max Planck Institute for Molecular Biomedicine, Germany
  2. University of Münster, Germany

Abstract

The blood-brain barrier (BBB) limits the entry of leukocytes and potentially harmful substances from the circulation into the central nervous system (CNS). While BBB defects are a hallmark of many neurological disorders, the cellular heterogeneity at the neurovascular interface and the mechanisms governing neuroinflammation are not fully understood. Through single cell RNA sequencing of non-neuronal cell populations of the murine cerebral cortex during development, adulthood, ageing and neuroinflammation, we identify reactive endothelial venules (REVs), a compartment of specialised post-capillary endothelial cells (ECs) that are characterized by consistent expression of cell adhesion molecules, preferential leukocyte transmigration, association with perivascular macrophage populations, and endothelial activation initiating CNS immune responses. Our results provide novel insights into the heterogeneity of the cerebral vasculature and a useful resource for the molecular alterations associated with neuroinflammation and ageing.

Data availability

Raw data (fastq files) and processed data (gene counts) for single cell RNA-Seq analysis have been deposited in the Gene Expression Omnibus with the primary accession number, GSE133283.

The following data sets were generated

Article and author information

Author details

  1. Hyun-Woo Jeong

    Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, Germany
    For correspondence
    hyun-woo.jeong@mpi-muenster.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6976-6739
  2. Rodrigo Diéguez-Hurtado

    Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2055-599X
  3. Hendrik Arf

    Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2038-705X
  4. Jian Song

    Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Hongryeol Park

    Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Kai Kruse

    Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Lydia Sorokin

    Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7704-7921
  8. Ralf H Adams

    Department of Tissue Morphogenesis, Max Planck Institute for Molecular Biomedicine, Münster, Germany
    For correspondence
    ralf.adams@mpi-muenster.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3031-7677

Funding

Max-Planck-Gesellschaft

  • Ralf H Adams

Deutsche Forschungsgemeinschaft (cluster of excellence Cells in Motion"")

  • Lydia Sorokin

Deutsche Forschungsgemeinschaft (CRC 1366)

  • Ralf H Adams

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Victoria L Bautch, University of North Carolina, Chapel Hill, United States

Ethics

Animal experimentation: All animal experiments were performed in compliance with the relevant laws and institutional guidelines, approved by local animal ethics committees, and conducted with permissions (84-02.04.2016.A525, 81-02.04.2020.A471 and 84-02.04.2017.A322) granted by the Landesamt für Natur, Umwelt und Verbraucherschutz (LANUV) of North Rhine-Westphalia, Germany. Every effort was made to minimize suffering.

Version history

  1. Received: April 2, 2020
  2. Preprint posted: June 13, 2022 (view preprint)
  3. Accepted: October 4, 2022
  4. Accepted Manuscript published: October 5, 2022 (version 1)
  5. Version of Record published: October 14, 2022 (version 2)

Copyright

© 2022, Jeong et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Hyun-Woo Jeong
  2. Rodrigo Diéguez-Hurtado
  3. Hendrik Arf
  4. Jian Song
  5. Hongryeol Park
  6. Kai Kruse
  7. Lydia Sorokin
  8. Ralf H Adams
(2022)
Single cell transcriptomics reveals functionally specialized vascular endothelium in brain
eLife 11:e57520.
https://doi.org/10.7554/eLife.57520

Share this article

https://doi.org/10.7554/eLife.57520

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