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Regional heterogeneity of the blood-brain barrier

Author

Listed:
  • Marie Blanchette

    (San Diego)

  • Kaja Bajc

    (San Diego)

  • Benjamin D. Gastfriend

    (San Diego
    University of Wisconsin–Madison)

  • 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
    Université Laval)

  • Louise Reveret

    (Centre de recherche du CHU de Québec-Université Laval
    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
    Université Laval)

  • Nina Isoherranen

    (University of Washington)

  • Sean P. Palecek

    (University of Wisconsin–Madison)

  • Eric V. Shusta

    (University of Wisconsin–Madison
    University of Wisconsin–Madison)

  • Jiaqian Wu

    (UTHealth)

  • Richard Daneman

    (San Diego)

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.

Suggested Citation

  • 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 , 2025. "Regional heterogeneity of the blood-brain barrier," Nature Communications, Nature, vol. 16(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61841-8
    DOI: 10.1038/s41467-025-61841-8
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