Soutenance de thèse Robin Canac

Equipe

Team II - Ion channels and cardiopathies

Directrice de thèse

Patricia Lemarchand

Co-encadrante

Nathalie Gaborit

Co-encadrant

Jérémie Poschmann


Rapporteurs

Examinateurs

Pr Delphine Potier, PhD - Centre d'Immunologie de Marseille-Luminy, Marseille
Pr Thomas Moore-Morris, PhD - Institut de Génomique Fonctionnelle, Montpellier

Abstract

Transcription factors are key elements in cardiac development, governing the establishment of a specific gene expression program. The chronological sequence of steps in the establishment of this program is controlled by a network of dynamic and temporal regulations of cardiac transcription factors. However, a global view of this network has not yet been obtained. Moreover, some transcription factors, such as those of the Iroquois family, which have been shown to be important in the heart, have not been analyzed or only to a limited extent in the context of networks with other cardiac transcription factors. By a transcriptomic analysis of the cardiac differentiation of human induced pluripotent stem cells, used as a model of human cardiac development, we identified on one hand, a global regulatory network between the transcription factors involved in the process. On the other hand, we identified a previously unknown role of the Iroquois transcription factors, IRX3 and IRX5, in the regulation of the expression and activity of major cardiac transcription factors, GATA4, TBX5 and NKX2-5. Then, a focused study on IRX5 allowed a better understanding of the role of its protein domains, its mechanisms of interaction and regulation of DNA, and the biological functions it regulates in cardiomyocyte differentiation. This study offers a better understanding of the molecular mechanisms of cardiac development and can also serve as a basis for the study of pathologies or for the development of new therapies.