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Publication : Characteristics of blood-brain barrier heterogeneity between brain regions revealed by profiling vascular and perivascular cells.

First Author  Pfau SJ Year  2024
Journal  Nat Neurosci Volume  27
Issue  10 Pages  1892-1903
PubMed ID  39210068 Mgi Jnum  J:358096
Mgi Id  MGI:7779721 Doi  10.1038/s41593-024-01743-y
Citation  Pfau SJ, et al. (2024) Characteristics of blood-brain barrier heterogeneity between brain regions revealed by profiling vascular and perivascular cells. Nat Neurosci 27(10):1892-1903
abstractText  The blood-brain barrier (BBB) protects the brain and maintains neuronal homeostasis. BBB properties can vary between brain regions to support regional functions, yet how BBB heterogeneity occurs is poorly understood. Here, we used single-cell and spatial transcriptomics to compare the mouse median eminence, one of the circumventricular organs that has naturally leaky blood vessels, with the cortex. We identified hundreds of molecular differences in endothelial cells (ECs) and perivascular cells, including astrocytes, pericytes and fibroblasts. Using electron microscopy and an aqueous-based tissue-clearing method, we revealed distinct anatomical specializations and interaction patterns of ECs and perivascular cells in these regions. Finally, we identified candidate regionally enriched EC-perivascular cell ligand-receptor pairs. Our results indicate that both molecular specializations in ECs and unique EC-perivascular cell interactions contribute to BBB functional heterogeneity. This platform can be used to investigate BBB heterogeneity in other regions and may facilitate the development of central nervous system region-specific therapeutics.
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