Molecular profiling of brain endothelial cell to astrocyte endfoot communication in mouse and human
Steven A. Hill,
Isabel Bravo-Ferrer,
Austėja Čiulkinytė,
Noelia Pérez Ramos,
Ilaria Rossetti,
Chiara Colvin,
Paula Beltran-Lobo,
Carlos Parra-Pérez,
Katie Emelianova,
Owen Dando,
Beth Geary,
Raja S. Nirujogi,
Dario R. Alessi,
Do-Young Lee,
Youn-Bok Lee and
Blanca Díaz Castro ()
Additional contact information
Steven A. Hill: Chancellor’s Building
Isabel Bravo-Ferrer: Chancellor’s Building
Austėja Čiulkinytė: Chancellor’s Building
Noelia Pérez Ramos: Chancellor’s Building
Ilaria Rossetti: Chancellor’s Building
Chiara Colvin: Chancellor’s Building
Paula Beltran-Lobo: Chancellor’s Building
Carlos Parra-Pérez: Chancellor’s Building
Katie Emelianova: Chancellor’s Building
Owen Dando: Chancellor’s Building
Beth Geary: University of Dundee
Raja S. Nirujogi: University of Dundee
Dario R. Alessi: University of Dundee
Do-Young Lee: King’s College London
Youn-Bok Lee: King’s College London
Blanca Díaz Castro: Chancellor’s Building
Nature Communications, 2025, vol. 16, issue 1, 1-24
Abstract:
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.
Date: 2025
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-65487-4
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DOI: 10.1038/s41467-025-65487-4
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