High-resolution single-cell transcriptomic survey of cardiomyocytes from patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is a common inherited cardiovascular disease, which can cause heart failure and lead to death. In this study, we performed high-resolution single-cell RNA-sequencing of 2115 individual cardiomyocytes obtained from HCM patients and normal controls. Signature up- and down-regulated genes in HCM were identified by integrative analysis across 37 patients and 41 controls from our data and published human single-cell and single-nucleus RNA-seq datasets, which were further classified into gene modules by single-cell co-expression analysis. Using our high-resolution dataset, we also investigated the heterogeneity among individual cardiomyocytes and revealed five distinct clusters within HCM cardiomyocytes. Interestingly, we showed that some extracellular matrix (ECM) genes were up-regulated in the HCM cardiomyocytes, suggesting that they play a role in cardiac remodelling. Taken together, our study comprehensively profiled the transcriptomic programs of HCM cardiomyocytes and provided insights into molecular mechanisms underlying the pathogenesis of HCM.