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Molecular profiling of brain endothelial cell to astrocyte endfoot communication in mouse and human.

Author information

Affiliations

  • 1. Centre for Discovery Brain Sciences, The University of Edinburgh, Chancellor's Building, Edinburgh, United Kingdom.
      Authors
    • Hill SA 1
    • Bravo-Ferrer I 1
    • Čiulkinytė A 1
    • Pérez Ramos N 1
    • Rossetti I 1
    • Colvin C 1
    • Beltran-Lobo P 1
    • Parra-Pérez C 1
    • Emelianova K 1
    • Dando O 1
    • Díaz Castro B 1
    (11 authors)
  • 2. Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, School of Life Sciences, University of Dundee, Dundee, United Kingdom.
      Authors
    • Geary B 2
    • Nirujogi RS 2
    • Alessi DR 2
    (3 authors)
  • 3. Department of Basic and Clinical Neuroscience, Maurice Wohl Clinical Neuroscience, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
      Authors
    • Lee DY 3
    • Lee YB 3
    (2 authors)

Nature Communications, 06 Nov 2025, 16(1):9750
https://doi.org/10.1038/s41467-025-65487-4 PMID: 41198665 PMCID: PMC12592424

This article is in the Europe PMC Open access subset. Refer to the copyright information in the article for licensing details.
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Abstract 

Our understanding of how the body communicates with the brain to coordinate their functions is remarkably limited. At the blood-brain barrier (BBB), brain endothelial cells (BECs) are ideally positioned to mediate signaling between blood and brain parenchyma via direct communication with astrocyte perivascular processes (endfeet). We develop a method to define the mouse in vivo astrocyte endfoot proteome, which in combination with BEC-specific RNA-seq, reveal BEC to astrocyte endfoot ligand-receptor pairs that are modulated when mice are exposed to a peripheral inflammatory insult with lipopolysaccharide. We show that over 80% of these mouse BEC-endfoot ligand-receptor pairs are also found in the human BBB, with a subset of them differentially expressed in human multiple sclerosis or Alzheimer's disease compared to healthy individuals. Our findings reveal dynamic BEC-endfoot communication pathways that are relevant to human physiology and provide methodology and datasets for the translational study of BEC-astrocyte crosstalk in health and disease.

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Read article at publisher's site: https://doi.org/10.1038/s41467-025-65487-4

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    Funding 

    Funders who supported this work.

    Alzheimer's Research UK (ARUK) (1)

    • Grant ID: ARUK-ECRBF2023B-005

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    Alzheimer's Society (2)

    • Grant ID: 663

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    • Grant ID: 609

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    Medical Research Council (1)

    • Grant ID: MC_UU_00018/1

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    Royal Society (1)

    • Grant ID: RGS\R1\231330

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    Wellcome Trust (1)

    • Grant ID: 218493/Z/19/Z

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