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

Información del proyecto

FatTFIso

Identificador del acuerdo de subvención: 898792

DOI

10.3030/898792

Proyecto finalizado el 31 Agosto 2020

Fecha de la firma de la CE 21 Febrero 2020

Fecha de inicio 1 Marzo 2020

Fecha de finalización 28 Febrero 2022

Financiado con arreglo a

• EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions

Coste total

€ 203 149,44

Aportación de la UE

€ 203 149,44

Coordinado por

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)

Período documentado: 2020-03-01 hasta 2022-02-28

Resumen del contexto y de los objetivos generales del proyecto

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.

Trabajo realizado desde el comienzo del proyecto hasta el final del período abarcado por el informe y los principales resultados hasta la fecha

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

Avances que van más allá del estado de la técnica e impacto potencial esperado (incluida la repercusión socioeconómica y las implicaciones sociales más amplias del proyecto hasta la fecha)

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