Characterizing the roles of transcription factor isoforms in rewiring gene regulatory networks during adipogenesis

Informations projet

FatTFIso

N° de convention de subvention: 898792

DOI

10.3030/898792

Projet clôturé le 31 Août 2020

Date de signature de la CE 21 Février 2020

Date de début 1 Mars 2020

Date de fin 28 Février 2022

Financé au titre de

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coût total

€ 203 149,44

Contribution de l’UE

€ 203 149,44

Coordonné par

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
Switzerland

Periodic Reporting for period 1 - FatTFIso (Characterizing the roles of transcription factor isoforms in rewiring gene regulatory networks during adipogenesis)

Période du rapport: 2020-03-01 au 2022-02-28

Résumé du contexte et des objectifs généraux du projet

Metabolism-related disorders pose a major global disease burden, as the rate of obesity rises worldwide. Fat tissue is a key site of metabolic regulation, and understanding how fat cells (adipocytes) develop forms the foundation for designing effective therapeutic and intervention strategies. This proposal aimed to understand the gene regulatory network (GRN) underlying fat cell development (adipogenesis) and to which extent this GRN is modulated by transcription factor (TF) isoforms. Adipogenesis is regulated by a network of successively activated TFs. Many of these TFs exist as multiple isoforms, a handful of which are known to function divergently from their reference forms. Most functional characterization studies have been restricted to gene-level studies, largely ignoring isoforms. Because TFs function at critical steps in adipogenesis, such functionally different isoforms could determine the difference between cells that differentiate into mature fat cells and those that remain in the precursor states. This project aimed to investigate the extent to which TF isoforms are functionally different in the context of adipogenesis by conducting two screens: an in vitro screen for TF isoforms demonstrating different DNA binding specificities using a microfluidics-based assay, and an in vivo screen for isoforms that alter adipocyte differentiation using a novel droplet-based single-cell technology assay. Findings from this project were expected to improve our understanding of transcriptional mechanisms in adipogenesis and have broad implications for the role of TF isoforms in gene regulation.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

Due to the early termination of this project in Month 6, only preliminary results for optimizing the in vitro screen were obtained.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

Due to the early termination of this project in Month 6, only preliminary results for optimizing the in vitro screen were obtained.