Characteristics of blood–brain barrier heterogeneity between brain regions revealed by profiling vascular and perivascular cells
Year: 2024
Type: article
Abstract: 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.
Source: Nature Neuroscience
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $12,290
Funders: Howard Hughes Medical Institute, U.S. Department of Health and Human Services, Damon Runyon Cancer Research Foundation, European Molecular Biology Organization, Allen Foundation, National Institutes of Health, National Institute on Drug Abuse, National Cancer Institute, National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G2445182664, G329596488, G3330643241, Studying perceptual decision-making across cortex by combining population imaging, connectomics, and computational modeling, HMS/BCH Center for Neuroscience Research, New tools for understanding the blood brain barrier, Validated tools for identifying, characterizing, and targeting all non-neuronal cells in the brain and determining the neuro-glio-vascular connectome, Novel EM technologies for imaging neural network anatomy, TissueCyte 1600FC Whole Mount Tissue Scanner, G7294706999, G8882010636, Boston Children's Hospital/HMS Intellectual and Developmental Disabilities Research Center, Molecular Mechanisms of the Blood Brain Barrier Function and Regulation
OpenAlex ID: W4402006981