A04: Modelling and decoding the mechanisms of left ventricular non compaction cardiomyopathy

Human left ventricular non-compaction cardiomyopathy (LVNC-CM) is a common, yet understudied, heart disease. Many LVNC-CM mutations impact developmental genes, including LMNA, suggesting that these cardiomyopathies have a developmental origin. Here, state-of-the-art 3D left-ventricle organoids and genome engineering are combined to model LMNA mutations. The impact of patient mutations on the differentiation and function of the left ventricle will be characterized using single-cell genomics. The impact of stress on the contractile properties of mutant organoids will be assessed. A04 will thereby reveal the mechanisms by which LMNA mutations predispose and induce LVNC-CM.