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
- Blanca Díaz-Castro
2025-11-06
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.