hiPSC based models for Arrhythmogenic Cardiomyopathy: validation of RNA-seq data of hiPSC-CMs and set up of protocol for hiPSC-epicardial cells differentiation

Arrhythmogenic cardiomyopathy (ACM) is a genetic disease with incomplete penetrance and variable expression. It manifests as myocardial replacement with fibrosis, major ventricular arrhythmias, and impaired ventricular systolic function. This thesis can be divided into two parts: the first is the characterization of iPSC-cardiomyocytes, and the second is the optimization of the differentiation protocol and characterization for iPSC-epicardium. The validation of an RNA-seq dataset for human induced pluripotent stem cells-cardiomyocytes (iPSC-CMs) carrying the heterozygous DSG p.Q558X mutation, generated from a patient with ACM, and the associated isogenic control cells. In particular, genes that may be related to inflammation, another important hallmark of the disease, were tested. The second part focuses on optimizing a protocol for differentiation into hiPSCs of wild-type cells and characterizing expression.