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Updated: Jul 15, 2025
An Approach to Study Shape-Dependent Transcriptomics at a Single Cell Level
Published on: November 2, 2020
High-resolution single-cell transcriptomic survey of cardiomyocytes from patients with hypertrophic cardiomyopathy
Jiansen Lu1,2, Jie Ren1,2,3, Jie Liu4
1College of Life Sciences, Biomedical Pioneering Innovation Center, Ministry of Education Key Laboratory of Cell Proliferation and Differentiation, Beijing, China.
Insights
Hypertrophic cardiomyopathy (HCM) is an inherited heart disease. This study reveals key gene changes and cellular differences in HCM cardiomyocytes, uncovering potential molecular mechanisms driving the condition.
Area of Science:
- Cardiovascular Biology
- Genomics
- Single-cell analysis
Background:
- Hypertrophic cardiomyopathy (HCM) is a prevalent inherited cardiovascular disease.
- HCM can lead to heart failure and mortality.
- Understanding the molecular underpinnings of HCM is crucial for developing effective treatments.
Purpose of the Study:
- To comprehensively profile the transcriptomic landscape of cardiomyocytes in HCM.
- To identify key genes and molecular pathways involved in HCM pathogenesis.
- To investigate cellular heterogeneity within HCM cardiomyocytes.
Main Methods:
- High-resolution single-cell RNA-sequencing (scRNA-seq) of 2115 cardiomyocytes from HCM patients and controls.
- Integrative analysis of scRNA-seq and single-nucleus RNA-seq datasets.
- Single-cell co-expression analysis to classify gene modules.
- Identification of distinct cardiomyocyte clusters in HCM.
Main Results:
- Identified signature up- and down-regulated genes in HCM cardiomyocytes.
- Revealed five distinct cardiomyocyte clusters within the HCM group.
- Observed up-regulation of extracellular matrix (ECM) genes in HCM cardiomyocytes, suggesting a role in cardiac remodeling.
- Provided a comprehensive transcriptomic profile of HCM cardiomyocytes.
Conclusions:
- The study offers deep insights into the molecular mechanisms of HCM pathogenesis.
- Transcriptomic profiling highlights the role of specific genes and ECM components in HCM.
- Understanding cardiomyocyte heterogeneity is key to unraveling HCM complexity.
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.
