Regional heterogeneity of the blood-brain barrier
Abstract The blood-brain barrier (BBB), formed by specialized endothelial cells (ECs), regulates the extracellular composition of the central nervous system (CNS). Little is known about whether there are regional specializations of the BBB that may control the function of specific neural circuits. W...
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Nature Portfolio
2025-08-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61841-8 |
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| author | Marie Blanchette Kaja Bajc Benjamin D. Gastfriend Caterina P. Profaci Nadine Ruderisch Cayce E. Dorrier Guo Zhong Raquel Cuevas-Diaz Duran Sean S. Harvey Iris H. Garcia-Pak Lucija Pintarić Manon Leclerc Louise Reveret Vincent Émond Annette Wang Deepti Pant Linus T. Tsai Frédéric Calon Nina Isoherranen Sean P. Palecek Eric V. Shusta Jiaqian Wu Richard Daneman |
| author_facet | Marie Blanchette Kaja Bajc Benjamin D. Gastfriend Caterina P. Profaci Nadine Ruderisch Cayce E. Dorrier Guo Zhong Raquel Cuevas-Diaz Duran Sean S. Harvey Iris H. Garcia-Pak Lucija Pintarić Manon Leclerc Louise Reveret Vincent Émond Annette Wang Deepti Pant Linus T. Tsai Frédéric Calon Nina Isoherranen Sean P. Palecek Eric V. Shusta Jiaqian Wu Richard Daneman |
| author_sort | Marie Blanchette |
| collection | DOAJ |
| description | Abstract The blood-brain barrier (BBB), formed by specialized endothelial cells (ECs), regulates the extracellular composition of the central nervous system (CNS). Little is known about whether there are regional specializations of the BBB that may control the function of specific neural circuits. We use single cell RNA-seq to characterize ECs from nine CNS regions in male mice: cortex, hippocampus, cerebellum, spinal cord, striatum, thalamus, hypothalamus, midbrain, and medulla/pons. Although there is a core BBB transcriptional profile, there are significant regional specializations. Stra6, a retinoid transporter, is highly enriched in the BBB of the nucleus accumbens shell (ShNAc) and ventral cochlear nucleus, and is controlled by dietary vitamin A, through endothelial RARƔ. EC Stra6 regulates the deposition of retinoids specifically in the ShNAc and cochlear nucleus, and is required for the function of the ShNAc, in a retinoid-dependent manner. Thus regional specializations of the BBB can regulate the function of local brain regions. |
| format | Article |
| id | doaj-art-528b1e5f3318496c831de20dccb8e636 |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-528b1e5f3318496c831de20dccb8e6362025-08-20T03:05:06ZengNature PortfolioNature Communications2041-17232025-08-0116111410.1038/s41467-025-61841-8Regional heterogeneity of the blood-brain barrierMarie Blanchette0Kaja Bajc1Benjamin D. Gastfriend2Caterina P. Profaci3Nadine Ruderisch4Cayce E. Dorrier5Guo Zhong6Raquel Cuevas-Diaz Duran7Sean S. Harvey8Iris H. Garcia-Pak9Lucija Pintarić10Manon Leclerc11Louise Reveret12Vincent Émond13Annette Wang14Deepti Pant15Linus T. Tsai16Frédéric Calon17Nina Isoherranen18Sean P. Palecek19Eric V. Shusta20Jiaqian Wu21Richard Daneman22Departments of Pharmacology and Neurosciences, University of California, San DiegoDepartments of Pharmacology and Neurosciences, University of California, San DiegoDepartments of Pharmacology and Neurosciences, University of California, San DiegoDepartments of Pharmacology and Neurosciences, University of California, San DiegoAbbVieDepartments of Pharmacology and Neurosciences, University of California, San DiegoDepartment of Pharmaceutics, School of Pharmacy, University of WashingtonTecnologico de Monterrey, Escuela de Medicina y Ciencias de la SaludDepartments of Pharmacology and Neurosciences, University of California, San DiegoDepartments of Pharmacology and Neurosciences, University of California, San DiegoDepartments of Pharmacology and Neurosciences, University of California, San DiegoAxe Neurosciences, Centre de recherche du CHU de Québec-Université LavalAxe Neurosciences, Centre de recherche du CHU de Québec-Université LavalAxe Neurosciences, Centre de recherche du CHU de Québec-Université LavalDepartment of Medicine, Harvard Medical SchoolDepartment of Medicine, Harvard Medical SchoolDepartment of Medicine, Harvard Medical SchoolAxe Neurosciences, Centre de recherche du CHU de Québec-Université LavalDepartment of Pharmaceutics, School of Pharmacy, University of WashingtonDepartment of Chemical and Biological Engineering, University of Wisconsin–MadisonDepartment of Chemical and Biological Engineering, University of Wisconsin–MadisonDepartment of Neurosurgery & Center for Stem Cell and Regenerative Medicine, UTHealthDepartments of Pharmacology and Neurosciences, University of California, San DiegoAbstract The blood-brain barrier (BBB), formed by specialized endothelial cells (ECs), regulates the extracellular composition of the central nervous system (CNS). Little is known about whether there are regional specializations of the BBB that may control the function of specific neural circuits. We use single cell RNA-seq to characterize ECs from nine CNS regions in male mice: cortex, hippocampus, cerebellum, spinal cord, striatum, thalamus, hypothalamus, midbrain, and medulla/pons. Although there is a core BBB transcriptional profile, there are significant regional specializations. Stra6, a retinoid transporter, is highly enriched in the BBB of the nucleus accumbens shell (ShNAc) and ventral cochlear nucleus, and is controlled by dietary vitamin A, through endothelial RARƔ. EC Stra6 regulates the deposition of retinoids specifically in the ShNAc and cochlear nucleus, and is required for the function of the ShNAc, in a retinoid-dependent manner. Thus regional specializations of the BBB can regulate the function of local brain regions.https://doi.org/10.1038/s41467-025-61841-8 |
| spellingShingle | Marie Blanchette Kaja Bajc Benjamin D. Gastfriend Caterina P. Profaci Nadine Ruderisch Cayce E. Dorrier Guo Zhong Raquel Cuevas-Diaz Duran Sean S. Harvey Iris H. Garcia-Pak Lucija Pintarić Manon Leclerc Louise Reveret Vincent Émond Annette Wang Deepti Pant Linus T. Tsai Frédéric Calon Nina Isoherranen Sean P. Palecek Eric V. Shusta Jiaqian Wu Richard Daneman Regional heterogeneity of the blood-brain barrier Nature Communications |
| title | Regional heterogeneity of the blood-brain barrier |
| title_full | Regional heterogeneity of the blood-brain barrier |
| title_fullStr | Regional heterogeneity of the blood-brain barrier |
| title_full_unstemmed | Regional heterogeneity of the blood-brain barrier |
| title_short | Regional heterogeneity of the blood-brain barrier |
| title_sort | regional heterogeneity of the blood brain barrier |
| url | https://doi.org/10.1038/s41467-025-61841-8 |
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