Related Experiment Video
Updated: Aug 19, 2025
Visualizing Impairment of the Endothelial and Glial Barriers of the Neurovascular Unit during Experimental Autoimmune Encephalomyelitis In Vivo
Published on: March 26, 2019
Single-Cell Transcriptomics Identifies Brain Endothelium Inflammatory Networks in Experimental Autoimmune
Antoine Philippe Fournier1, Olivier Tastet1, Marc Charabati1
1From the Neuroimmunology Research Laboratory (A.P.F., O.T., M.C., C.H., L.B., W.K., S.L., F.T., C.L., N.A., S.Z., A.P.), Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM); Department of Neurosciences (A.P.F., C.L., N.A., S.Z., A.P.), Faculty of Medicine, Université de Montréal; Multiple Sclerosis Clinic (C.L., A.P.), Division of Neurology, Centre Hospitalier de l'Université de Montréal (CHUM); Department of Human Genetics (J.R.), McGill University, Montréal; and McGill Genome Centre (Y.C.W., J.R.), Montréal, Québec, Canada.
Researchers identified key molecular changes in brain endothelial cells (ECs) during experimental multiple sclerosis (MS). Venous ECs showed significant alterations, suggesting a crucial role in immune cell infiltration across the blood-brain barrier in MS.
Area of Science:
- Neuroimmunology
- Vascular Biology
- Single-cell genomics
Background:
- Multiple sclerosis (MS) involves immune cell infiltration into the central nervous system (CNS) across the blood-brain barrier (BBB).
- The precise molecular mechanisms enabling immune cell entry into the CNS in MS remain incompletely understood.
Purpose of the Study:
- To characterize cellular heterogeneity and molecular processes in the CNS during experimental autoimmune encephalomyelitis (EAE), an animal model of MS.
- To identify specific endothelial cell (EC) populations and molecular interactions involved in neuroinflammation and immune cell trafficking.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) of enriched endothelial cells (ECs) from the EAE mouse model.
- Immunohistochemistry and confocal microscopy to validate gene and protein expression in human MS brain lesions.
Main Results:
- Upregulation of antigen presentation and interferon-related genes observed in CNS-resident cells, including ECs.
- A continuous gene expression gradient across the brain vasculature, with more transcriptomic alterations in venous ECs.
- Identification of potential ligand-receptor interactions between venous ECs and infiltrating immune cells.
- Validation of upregulated gene (Ackr1, Lcn2) protein expression in human MS lesions.
Conclusions:
- This study provides a comprehensive cellular and molecular landscape of neuroinflammation in EAE.
- Venous ECs play a significant role in immune cell infiltration into the CNS during MS.
- Identified molecular insights warrant further investigation into therapeutic strategies targeting the BBB in MS.
