Molecular profiling of brain endothelial cell to astrocyte endfoot communication in mouse and human
Year: 2025
Type: article
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.
Source: Nature Communications
Authors: 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, Blanca Díaz Castro
Institutions: British Heart Foundation, UK Dementia Research Institute, University of Edinburgh, University College London, Universidad Complutense de Madrid, Spanish National Centre for Cardiovascular Research, University of Vienna, Simons Initiative for the Developing Brain, University of Dundee, MRC Protein Phosphorylation and Ubiquitylation Unit, King's College London
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W4415954615