4.8 Article

Single-cell transcriptomics reveals functionally specialized vascular endothelium in brain

Journal

ELIFE
Volume 11, Issue -, Pages -

Publisher

eLIFE SCIENCES PUBL LTD
DOI: 10.7554/eLife.57520

Keywords

blood-brain barrier; vasculature; single-cell RNA sequencing; non-neuronal cell populations; Mouse

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Funding

  1. Max Planck Society
  2. University of Muenster
  3. German Research Foundation (DFG) [CRC1366A01, CRC1009A02, SO285/11-1, EXC1003]

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The blood-brain barrier restricts the entry of leukocytes and harmful substances into the central nervous system. However, the cellular heterogeneity at the neurovascular interface and the mechanisms of neuroinflammation are not fully understood. Through single-cell RNA sequencing, researchers identified a compartment of specialized endothelial cells called reactive endothelial venules, which are involved in CNS immune responses.
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.

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