Regional heterogeneity of the blood-brain barrier
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.
Authors
- Caterina P. Profaci (ORCID: https://orcid.org/0000-0002-4073-2164)
- Frédéric Calon (ORCID: https://orcid.org/0000-0002-4203-0887)
- Cayce Dorrier
- Benjamin D. Gastfriend (ORCID: https://orcid.org/0000-0002-4677-1455)
- Eric V. Shusta (ORCID: https://orcid.org/0000-0002-4297-0158)
- Linus Tsai (ORCID: https://orcid.org/0000-0002-0134-6949)
- Richard Daneman (ORCID: https://orcid.org/0000-0002-7749-6353)
- Nina Isoherranen (ORCID: https://orcid.org/0000-0002-9548-3126)
- Vincent Émond (ORCID: https://orcid.org/0009-0004-8931-5785)
- Raquel Cuevas‐Díaz Durán (ORCID: https://orcid.org/0000-0003-4257-3184)
- Louise Réveret
- Kaja Bajc
- Marie Blanchette (ORCID: https://orcid.org/0000-0003-1187-8700)
- Sean P. Palecek (ORCID: https://orcid.org/0000-0003-4917-5584)
- Sean Harvey (ORCID: https://orcid.org/0000-0002-2153-8235)
- Annette Wang
- Deepti Pant (ORCID: https://orcid.org/0000-0002-6890-081X)
- Lucija Pintarić (ORCID: https://orcid.org/0000-0003-4577-7334)
- Nadine Ruderisch
- Iris Garcia-Pak
- Guo Zhong (ORCID: https://orcid.org/0000-0001-7230-8336)
- Manon Leclerc (ORCID: https://orcid.org/0009-0009-5958-6599)
- Jiaqian Wu
Institutions
- University of Wisconsin–Madison (US)
- Harvard University (US)
- University of Washington (US)
- AbbVie (United States) (US)
- University of California San Diego (US)
- Institute for Stem Cell Biology and Regenerative Medicine (IN)
- Broad Center (US)
- Neurological Surgery (US)
- Université Laval (CA)
- Tecnológico de Monterrey (MX)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-08-08
- DOI
- https://doi.org/10.1038/s41467-025-61841-8
- Citations
- 4
- Primary Topic
- Neuroinflammation and Neurodegeneration Mechanisms
- Type
- article
- Field-Weighted Citation Impact
- 3.37
Funders
- National Science Foundation
- National Institutes of Health
- Center for AIDS Research, University of Washington
- University of California, San Diego
- University of California, San Francisco
- National Institute on Aging
- National Heart, Lung, and Blood Institute
- National Institute on Drug Abuse
- National Cancer Institute
- National Institute of General Medical Sciences
- National Institute of Allergy and Infectious Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Neurological Disorders and Stroke
- National Institute of Dental and Craniofacial Research
- National Institute on Minority Health and Health Disparities