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Building a metabolic atlas of human pluripotency: dissecting the interplay between pluripotency and metabolism in human stem cells.

Project description

The link between metabolism and pluripotency in human stem cells

Human pluripotent stem cells (hPSCs) are a type of stem cells that have the ability to differentiate into many different types of cells in the body. As these cells begin to differentiate, they undergo extensive transcriptional changes and metabolic transitions. Funded by the Marie Skłodowska-Curie Actions programme, the PLURImet project aims to study the role of JAK/STAT signaling in the transcriptional programme and metabolism of hPSCs. The project includes creating a computational model of hPSC metabolism to identify metabolic changes associated with pluripotency transitions. Using a highly interdisciplinary approach, the research will investigate the role of metabolism during the generation, expansion, and differentiation of naïve hPSCs.

Objective

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.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

UNIVERSITA DEGLI STUDI DI PADOVA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 172 750,08
Address
VIA 8 FEBBRAIO 2
35122 PADOVA
Italy

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Region
Nord-Est Veneto Padova
Activity type
Higher or Secondary Education Establishments
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Total cost

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