Description du projet
Le lien entre le métabolisme et la pluripotence dans les cellules souches humaines
Les cellules souches pluripotentes humaines (CSPh) se caractérisent par leur capacité à se différencier en de nombreux types de cellules dans l’organisme. Lorsqu’elles entament ce processus de différenciation, elles subissent d’importants changements transcriptionnels et des transitions métaboliques. Financé par le programme Actions Marie Skłodowska-Curie, le projet PLURImet vise à étudier le rôle de la signalisation JAK/STAT dans le programme transcriptionnel et le métabolisme des CSPh. Il inclut la création d’un modèle informatique de ce métabolisme afin d’identifier les changements associés aux transitions de la pluripotence. En adoptant une approche hautement interdisciplinaire, la recherche portera sur le rôle du métabolisme au cours de la génération, de l’expansion et de la différenciation des CSPh naïves.
Objectif
The naïve inner cell mass of the human embryo is characterized by unlimited developmental plasticity as it gives rise to all somatic and extraembryonic lineages. Following implantation, extraembryonic and auto inductive signals prime pluripotent cells for differentiation toward the three germ layers. Concomitantly, metabolic gene expression transits from oxidative phosphorylation towards a glycolytic metabolism. This developmental progression can be recapitulated in vitro using human pluripotent stem cells (hPSCs), a prominent tool for basic and translational research with a great impact on health and economics. Ligands of the JAK/STAT pathway are routinely used for the expansion, generation, and differentiation of naïve hPSCs. In rodents, JAK/STAT signaling controls both pluripotency gene expression and metabolism, but its role in human pluripotency is still unclear. In this project, I will unravel the contribution JAK/STAT pathway to both the transcriptional program and metabolism of human naïve pluripotency. I will study the role of metabolism during the generation, expansion, and differentiation of naïve hPSCs. Moreover, I will produce the first comprehensive computational model of hPSC metabolism to identify metabolic changes associated with human pluripotency transitions. This study is highly interdisciplinary, including scientific expertise encompassing cellular and molecular biology, biophysics, high throughput technologies, and computational biology. The wide scientific and transferable skills training provided by the host institution will allow me to achieve personal and professional maturity, crucial for an independent and competitive scientific career in Europe. The variety of the dissemination and communication measures implemented will definitively ensure maximal reachability to the project, maximizing the scientific and social return of this research.
Champ scientifique
- natural sciencesbiological sciencescell biologycell signaling
- natural sciencesbiological sciencescell biologycell metabolism
- natural sciencesbiological sciencesdevelopmental biology
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- natural sciencesbiological sciencesmolecular biology
Mots‑clés
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régime de financement
MSCA-PF - MSCA-PFCoordinateur
35122 Padova
Italie