Description du projet
Une nouvelle étude examine les interactions qui perturbent la production de myéline
La perturbation de la production de myéline dans notre organisme entraîne de graves maladies, telles que la sclérose en plaques. Le projet OLI.VAS financé par l’UE, étudiera les interactions moléculaires entre les vaisseaux sanguins et les oligodendrocytes, des cellules gliales qui produisent la myéline dans le système nerveux central. Des recherches récentes indiquent que les vaisseaux sanguins non seulement fournissent de l’oxygène et des nutriments, mais qu’ils régulent activement le développement et la fonction des organes. À cet égard, les chercheurs d’OLI.VAS ont découvert que les signaux issus des vaisseaux contrôlent directement la génération de cellules précurseurs d’oligodendrocytes dans une interface «oligo-vasculaire». En adoptant une approche pluridisciplinaire, les chercheurs envisagent d’identifier les interactions moléculaires entre les vaisseaux sanguins et les oligodendrocytes pendant le développement et l’homéostasie, ainsi que dans les cas de maladies démyélinisantes.
Objectif
Oligodendrocytes (OLs) are the glia cells that produce myelin in the central nervous system (CNS). Despite the severe outcome of demyelinating diseases, like multiple sclerosis (MS), little is known about the mechanisms by which myelin is disrupted or why remyelination fails in disease. Thus, a substantial advance in the understanding of oligodendrocyte biology and myelin pathology is required in order to develop successful treatments for demyelinating diseases.
Recent research indicates that apart from delivering oxygen and nutrients, blood vessels are active regulators of organ function. Our recent work supports the existence of an oligo-vascular interface where vessels directly control oligodendrogenesis. However, mechanistic insights of the interaction between OLs and the vasculature are lacking. Based on the innovative hypothesis that proper generation and OL functionality depends on active crosstalk with the vasculature, the OLI.VAS project will now tackle the challenge to characterize in depth the interaction between OLs and the vasculature during development and demyelinating diseases.
To achieve this goal, two complementary multidisciplinary research tracks are pursued:
Research track 1: Deconstructing and reconstructing the oligo-vascular interface to unravel the relationship of oligodendrocyte lineage cells with the vasculature
Research track 2: Studying the oligo-vascular interface in white matter lesions. Modulating the vasculature to prevent de-myelination or promote of re-myelination
Both tracks combine cutting edge technology in single cell and spatial transcriptomics, bioinformatics, 3D imaging, in vitro and ex vivo tissue culture, mouse genetics and MS patient samples.
OLI.VAS will deliver new insights into the role of the vasculature as a regulator of oligodendrogenesis and myelination and thus generate major scientific breakthroughs in an area that is highly relevant for diseases such as MS, which affects more than 600000 patients in Europe.
Champ scientifique
Mots‑clés
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
53127 Bonn
Allemagne