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

Abstract

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.