Single cell transcriptomics reveals functionally specialized vascular endothelium in brain
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.
Article and author information
Author details
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.
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.
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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