Regional heterogeneity of the blood-brain barrier

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 and Richard Daneman ()
Additional contact information
Marie Blanchette: San Diego
Kaja Bajc: San Diego
Benjamin D. Gastfriend: San Diego
Caterina P. Profaci: San Diego
Nadine Ruderisch: AbbVie
Cayce E. Dorrier: San Diego
Guo Zhong: University of Washington
Raquel Cuevas-Diaz Duran: Escuela de Medicina y Ciencias de la Salud
Sean S. Harvey: San Diego
Iris H. Garcia-Pak: San Diego
Lucija Pintarić: San Diego
Manon Leclerc: Centre de recherche du CHU de Québec-Université Laval
Louise Reveret: Centre de recherche du CHU de Québec-Université Laval
Vincent Émond: Centre de recherche du CHU de Québec-Université Laval
Annette Wang: Harvard Medical School
Deepti Pant: Harvard Medical School
Linus T. Tsai: Harvard Medical School
Frédéric Calon: Centre de recherche du CHU de Québec-Université Laval
Nina Isoherranen: University of Washington
Sean P. Palecek: University of Wisconsin–Madison
Eric V. Shusta: University of Wisconsin–Madison
Jiaqian Wu: UTHealth
Richard Daneman: San Diego

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-61841-8

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