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.
Metrics
-
- 7,074
- views
-
- 1,244
- downloads
-
- 45
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Developmental Biology
Cells called alveolar myofibroblasts, which have a central role in the development of the lung after birth, receive an orchestrated input from a range of different signaling pathways.
-
- Developmental Biology
We have generated single cell transcriptomic atlases of vomeronasal organs (VNO) from juvenile and adult mice. Combined with spatial molecular imaging, we uncover a distinct, previously unidentified class of cells that express the vomeronasal receptors (VRs) and a population of canonical olfactory sensory neurons in the VNO. High-resolution trajectory and cluster analyses reveal the lineage relationship, spatial distribution of cell types, and a putative cascade of molecular events that specify the V1r, V2r, and OR lineages from a common stem cell population. The expression of vomeronasal and olfactory receptors follow power law distributions, but there is high variability in average expression levels between individual receptor and cell types. Substantial co-expression is found between receptors across clades, from different classes, and between olfactory and VRs, with nearly half from pairs located on the same chromosome. Interestingly, the expression of V2r, but not V1r, genes is associated with various transcription factors, suggesting distinct mechanisms of receptor choice associated with the two cell types. We identify association between transcription factors, surface axon guidance molecules, and individual VRs, thereby uncovering a molecular code that guides the specification of the vomeronasal circuitry. Our study provides a wealth of data on the development and organization of the accessory olfactory system at both cellular and molecular levels to enable a deeper understanding of vomeronasal system function.