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Single-cell atlas of the human brain vasculature across development, adulthood and disease.
- Source :
-
Nature [Nature] 2024 Aug; Vol. 632 (8025), pp. 603-613. Date of Electronic Publication: 2024 Jul 10. - Publication Year :
- 2024
-
Abstract
- A broad range of brain pathologies critically relies on the vasculature, and cerebrovascular disease is a leading cause of death worldwide. However, the cellular and molecular architecture of the human brain vasculature remains incompletely understood <superscript>1</superscript> . Here we performed single-cell RNA sequencing analysis of 606,380 freshly isolated endothelial cells, perivascular cells and other tissue-derived cells from 117 samples, from 68 human fetuses and adult patients to construct a molecular atlas of the developing fetal, adult control and diseased human brain vasculature. We identify extensive molecular heterogeneity of the vasculature of healthy fetal and adult human brains and across five vascular-dependent central nervous system (CNS) pathologies, including brain tumours and brain vascular malformations. We identify alteration of arteriovenous differentiation and reactivated fetal as well as conserved dysregulated genes and pathways in the diseased vasculature. Pathological endothelial cells display a loss of CNS-specific properties and reveal an upregulation of MHC class II molecules, indicating atypical features of CNS endothelial cells. Cell-cell interaction analyses predict substantial endothelial-to-perivascular cell ligand-receptor cross-talk, including immune-related and angiogenic pathways, thereby revealing a central role for the endothelium within brain neurovascular unit signalling networks. Our single-cell brain atlas provides insights into the molecular architecture and heterogeneity of the developing, adult/control and diseased human brain vasculature and serves as a powerful reference for future studies.<br /> (© 2024. Crown.)
- Subjects :
- Female
Humans
Male
Cell Communication
HLA-D Antigens metabolism
Adult
Health
Brain blood supply
Brain pathology
Brain embryology
Brain metabolism
Brain Neoplasms blood supply
Brain Neoplasms pathology
Endothelial Cells metabolism
Endothelial Cells pathology
Endothelial Cells cytology
Fetus blood supply
Fetus cytology
Fetus embryology
RNA-Seq
Single-Cell Gene Expression Analysis
Central Nervous System Vascular Malformations pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1476-4687
- Volume :
- 632
- Issue :
- 8025
- Database :
- MEDLINE
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 38987604
- Full Text :
- https://doi.org/10.1038/s41586-024-07493-y