Year 2

Overall, we have been able to achieve the milestones proposed for Year 2 of the grant. We have generated a panel of control and ARVC hiPSC lines using integration-free based methods. We provide evidence of our method to generate robust numbers of hiPSC-derived cardiac cells that express desmosomal cell-cell junction proteins. We show ARVC lines that display disease symptom-specific features (adipogenic or arrhythmic), which phenocopy the striking and differential symptoms found in respective individual ARVC-patients as tools to study human ARVC. We also uncover desmosomal defects in hiPSC-derived cardiac muscle cells that underlie the disease features found in ARVC cells. We have also published two reviews in the field of cell-cell junctional remodeling and stem cell approaches that helps to further our understanding of this field in cardiomyocytes, that is relevant to human disease and our research using hiPS.