WP4 objectives: 1) Characterize the transcriptome of individual cells from patients with pathogenic variants and cardiac dysfunction ranging from early to end-stage to model the continuum of heart failure. 2) Perform single-nucleus RNAsequencing (snRNA-seq) for in-depth characterisation of cardiac cell populations and their interactions / communication in endomyocardial biopsies of these patients and in murine models of DCM. 3) Discern fundamental mechanisms of maladaptive cardiac remodelling at distinct disease stages.
Endocardial biopsies from selected patient samples will be analysed using snRNA-seq. Using snRNA-seq data, we will perform cardiac cell- type and state resolved analyses to characterize cellular composition, gene expression differences and cellular circuits comparing healthy and patient hearts across the spectrum from early to end stage DCM. We will complement our studies in mouse DCM models at different time points during disease progression and compare findings in additional mouse lines.