AG Konze

AG Konze, MHH, MZP
AG Konze, MHH, MZP

Cardiomyocytes from human induced pluripotent stem cells as a cellular model for hypertrophic cardiomyopathy

 

Research focus

 

The focus of our research is the analysis of human induced pluripotent stem cell (hiPSCs)-derived cardiomyocytes (hiPSC-CMs) carrying mutations in the cardiac myosin-binding protein C (cMyBP-C). Mutations in cMyBP-C are besides mutations in beta-cardiac myosin (MyHC) the most frequent genetic cause for hypertrophic cardiomyopathy (HCM). HCM is a severe disease of the heart, which is mostly characterised by thickening of the interventricular septum and the left ventricular wall. On the microscopic level, typically there is fibrosis and a loss of cardiomyocyte alignment (disarray). These alterations lead to progressive heart failure, but can also cause arrhythmias and sudden cardiac death.

In our group, we analyse in a DFG-funded project several hiPSCs with different mutations in cMyBP-C to achieve a better understanding of the molecular mechanisms leading to HCM. Our hypothesis is that unequal contractile properties of neighboring cardiomyocytes (“contractile imbalance”) lead or contribute to the development of disarray and fibrosis. Mechanisms that lead to contractile imbalance will be characterised here in a cellular model

The hiPSC-CMs are being generated with high purity in cooperation with the group of PD Dr. Robert Zweigerdt, LEBAO, MHH, and are further cultivated with our established maturation protocols to achieve a homogenous cardiomyocyte population with regard to different maturation markers, such as beta-MyHC. The matured cardiomyocytes are then screened for potential differences in gene expression, contractile features, calcium transients and alignment of myofibrils between hiPSCs-CMs with and without cMyBP-C mutations. We apply several state-of-the-art methods such as transcriptomics, MyoCam measurements, immunofluorescence microscopy and live cell microscopy.