Single-cell transcriptomics reveals functionally specialized vascular endothelium in brain

Elife. 2022 Oct 5:11:e57520. doi: 10.7554/eLife.57520.


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, a compartment of specialized postcapillary endothelial cells 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.

Keywords: blood-brain barrier; developmental biology; immunology; inflammation; mouse; non-neuronal cell populations; single-cell RNA sequencing; vasculature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism
  • Brain / metabolism
  • Cell Adhesion Molecules / metabolism
  • Endothelial Cells* / metabolism
  • Endothelium, Vascular* / metabolism
  • Mice
  • Transcriptome


  • Cell Adhesion Molecules

Associated data

  • GEO/GSE133283

Grants and funding

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