Description du projet
Lever le voile sur les propriétés des cellules souches neurales
Les cellules souches neuronales (CSN) sont un type spécialisé de cellules souches qui peuvent engendrer divers types de cellules présentes dans le système nerveux, notamment les neurones, les astrocytes et les oligodendrocytes. Malgré leur rôle prometteur pour la maintenance et la réparation du système nerveux, leur hétérogénéité a empêché la parfaite compréhension de leur «caractère souche». Financé par le Conseil européen de la recherche, le projet PEPS entend faire la lumière sur les complexités et le potentiel des populations de CSN dans le cerveau des vertébrés. Les chercheurs partent de l’hypothèse que les interactions spatio-temporelles entre ces diverses CSN coordonnent leur comportement. Les résultats du projet sur le «caractère souche» feront progresser notre compréhension des CSN et du développement du système nerveux.
Objectif
Neural stem cell (NSC) populations in the vertebrate brain generate adult-born neurons for plasticity, growth, and repair. Neurogenic and gliogenic capacity, based on long-term NSC maintenance, functionally define “stemness”. Stemness embodies massive NSC heterogeneity at the single cell level and requires control of maintenance or differentiation decisions at the population level. These features remain mechanistically unreconciled. We hypothesise that spatiotemporal interactions among heterogeneous NSCs are coordinated to control the population behaviour. Thus, we propose a multi-dimensional project exploring these features in time and space, to decode the mechanistic principles of stemness. To this end, we bring together experimental and theoretical groups with complementary expertise in NSC biology, biostatistics and mathematical modelling. In an iterative experimental-mathematical approach, we will (1) solve the topology of individual NSC trajectories in transcriptomic space, (2) identify local cell-cell coordination mechanisms that impact these trajectories in situ, and (3) decode the resulting systemic properties and outputs of NSC ensembles at long-term and large spatial scales. This programme will result in original methods, including retrospective transcriptomics in single cells, innovative barcode transfers, and a novel mathematical framework to describe structured spatio-temporal population dynamics. We will focus on two biological model systems, the adult mouse ventricular sub-ventricular zone and zebrafish pallium, where NSC ensembles display comparable heterogeneity but differ in spatial organisation and fate dynamics. Together, PEPS will uncover the general principles and regulatory mechanisms of perpetuating stemness in time and space. It will lay the conceptual and methodological foundation to manipulate stem cell systems to improve their stability or output, and also produce new methods of universal value for studying cellular systems.
Champ scientifique
Mots‑clés
- adult neural stem cells
- zebrafish pallium
- ventricular-subventricular zone
- spatio-temporal population dynamics
- single-cell multi-omics
- Barcoded-transfer connectome
- Brain injury
- Single-cell perturbations
- mathematical modelling
- structured population models
- partial differential equation
- high dimensional statistics
- dimension reduction
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thème(s)
Régime de financement
HORIZON-ERC-SYG - HORIZON ERC Synergy GrantsInstitution d’accueil
69120 Heidelberg
Allemagne