• Le 22 June 2022
    Amphi Denis Escande
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  • 14 h 30

Titre de la thèse : Molecular pathophysiology of Brugada syndrome during cardiac development


Team II - Ion Channels and Cardiopathies

Directeur de thèse

Richard Redon


Guillaume Lamirault


Loredana Martignetti, PhD, Inserm U900/Institut Curie/Mines ParisTech, Paris
Francesca Rochais, PhD, Marseille Medical Genetics


Patricia Lemarchand, MD, PhD, Nantes, Inserm U1087
Fabienne Lescroart, PhD, Marseille Medical Genetics
Vincent Probst, MD, PhD, Nantes, Inserm U1087
Sylvain Richard, PhD, Inserm U1046, CNRS UMR 9214, Université de Montpellier


Recent genetic data suggest that pathogenesis of Brugada syndrome (BrS), an inherited arrhythmia responsible for sudden cardiac death in young adults can be linked to cardiac development abnormalities. Using human induced pluripotent stem cells (hiPSCs) cardiac differentiation model, the aim of this work is to better understand the pathological molecular mechanisms leading to BrS.

Through the generation and analysis of kinetic transcriptomic data during cardiac differentiation of control hiPSCs lines, we demonstrated that this in vitro model mimics the key steps of cardiac development. With a system biology approach we predicted the transcription factor regulatory network governing gene expression during cardiac differentiation. This work validates that this model is relevant to study human cardiac development and provides new insight in the regulatory mechanisms governing human cardiac development.

Subsequently, generation and analysis of transcriptomic data during cardiac differentiation of BrS hiPSCs lines identified patient-specific gene expression signatures arising during cardiac differentiation of hiPSCs, reinforcing the hypothesis of a developmental origin for BrS. Together, these results contribute to a better understanding of the molecular mechanisms leading to BrS and pave the way for further identification a new therapeutic targets.