Descripción del proyecto
El vínculo entre metabolismo y pluripotencia en células madre humanas
Las células madre pluripotentes humanas (CMPh) son una clase de células madre con la capacidad de diferenciarse en muchos tipos diferentes de células del organismo. A medida que se diferencian, experimentan grandes cambios transcripcionales y transiciones metabólicas. El objetivo del proyecto PLURImet, financiado por las Acciones Marie Skłodowska-Curie, es estudiar el papel de la señalización JAK/STAT en el programa transcripcional y el metabolismo de las CMPh. En el proyecto se incluye la creación de un modelo informático del metabolismo de las CMPh a fin de identificar los cambios metabólicos relacionados con las transiciones de pluripotencia. Su equipo empleará un planteamiento interdisciplinario para investigar el papel del metabolismo durante la generación, expansión y diferenciación de las CMPh indiferenciadas.
Objetivo
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.
Ámbito científico
- 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
Palabras clave
Programa(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Régimen de financiación
MSCA-PF - MSCA-PFCoordinador
35122 Padova
Italia