Molecular profiling of brain endothelial cell to astrocyte endfoot communication in mouse and human
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.
Authors
- Raja Sekhar Nirujogi (ORCID: https://orcid.org/0000-0002-3177-8566)
- Paula Beltran-Lobo (ORCID: https://orcid.org/0009-0006-2499-7740)
- Owen Robert Dando (ORCID: https://orcid.org/0000-0002-6269-6408)
- Blanca Díaz‐Castro (ORCID: https://orcid.org/0000-0003-1839-985X)
- Ilaria Rossetti (ORCID: https://orcid.org/0000-0002-9081-8783)
- Daseul Lee
- Dario R. Alessi (ORCID: https://orcid.org/0000-0002-2140-9185)
- Bethany Geary (ORCID: https://orcid.org/0000-0002-5592-5532)
- Youn‐Bok Lee (ORCID: https://orcid.org/0000-0002-0479-9361)
- Nadine Ramos (ORCID: https://orcid.org/0009-0002-8305-791X)
- Katie Emelianova (ORCID: https://orcid.org/0000-0002-5981-4442)
- Isabel Bravo‐Ferrer (ORCID: https://orcid.org/0000-0003-4566-2617)
- Austėja Čiulkinytė (ORCID: https://orcid.org/0000-0001-5268-5492)
- Steven Hill (ORCID: https://orcid.org/0000-0002-8903-4551)
- Carlos Parra-Pérez (ORCID: https://orcid.org/0009-0007-3817-1445)
- Chiara Colvin
Institutions
- Universidad Complutense de Madrid (ES)
- University of Vienna (AT)
- University of Dundee (GB)
- King's College London (GB)
- Spanish National Centre for Cardiovascular Research (ES)
- MRC Protein Phosphorylation and Ubiquitylation Unit (GB)
- UK Dementia Research Institute (GB)
- University College London (GB)
- Medical Research Council (GB)
- University of Edinburgh (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-11-06
- DOI
- https://doi.org/10.1038/s41467-025-65487-4
- Citations
- 4
- Primary Topic
- Barrier Structure and Function Studies
- Type
- article
- Field-Weighted Citation Impact
- 3.37
Funders
- Wellcome Trust
- Alzheimer's Society
- Royal Society
- UK Dementia Research Institute
- Medical Research Council