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Updated: Sep 23, 2025
An Approach to Study Shape-Dependent Transcriptomics at a Single Cell Level
Published on: November 2, 2020
Single-cell transcriptomics provides insights into hypertrophic cardiomyopathy
Martijn Wehrens1, Anne E de Leeuw1, Maya Wright-Clark2
1Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW) and University Medical Center, Utrecht, the Netherlands.
Insights
Hypertrophic cardiomyopathy (HCM) research reveals gene networks driving heart cell growth. This study uses single-cell RNA sequencing to uncover molecular insights for improved HCM therapies.
Area of Science:
- Cardiovascular Medicine
- Genetics
- Molecular Biology
Background:
- Hypertrophic cardiomyopathy (HCM) is a genetic heart disease causing unexplained heart muscle thickening, often in the septum.
- While sarcomeric gene mutations are common causes, the mechanisms behind heterogeneous cardiac remodeling in HCM are not fully understood.
- Improved understanding of gene networks controlling cardiomyocyte (CM) hypertrophy is crucial for developing effective HCM therapies.
Purpose of the Study:
- To investigate the molecular mechanisms underlying cardiomyocyte hypertrophy in human hypertrophic cardiomyopathy.
- To identify functional links between genes, transcription factors, and cell size in HCM using patient-derived samples.
- To explore the utility of single-cell RNA sequencing for studying the hypertrophic human heart.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) was performed on septal myectomy samples from patients with HCM.
- Analysis focused on identifying gene networks, transcription factors, and cell size correlations relevant to HCM.
- scRNA-seq data was used to characterize cardiomyocyte heterogeneity and molecular events in the hypertrophic heart.
Main Results:
- scRNA-seq successfully provided insights into the molecular landscape of the human hypertrophic heart.
- Significant heterogeneity was observed among cardiomyocytes in HCM samples.
- Functional links between specific genes, transcription factors, and cardiomyocyte size were identified, offering potential therapeutic targets.
Conclusions:
- Single-cell RNA sequencing is a valuable tool for dissecting molecular events in human hypertrophic cardiomyopathy.
- The study highlights cardiomyocyte heterogeneity and identifies key molecular players in HCM pathogenesis.
- Findings provide a foundation for developing targeted therapeutic strategies to improve treatment for HCM patients.
Abstract:
Hypertrophic cardiomyopathy (HCM) is a genetic heart disease that is characterized by unexplained segmental hypertrophy that is usually most pronounced in the septum. While sarcomeric gene mutations are often the genetic basis for HCM, the mechanistic origin for the heterogeneous remodeling remains largely unknown. A better understanding of the gene networks driving the cardiomyocyte (CM) hypertrophy is required to improve therapeutic strategies. Patients suffering from HCM often receive a septal myectomy surgery to relieve outflow tract obstruction due to hypertrophy. Using single-cell RNA sequencing (scRNA-seq) on septal myectomy samples from patients with HCM, we identify functional links between genes, transcription factors, and cell size relevant for HCM. The data show the utility of using scRNA-seq on the human hypertrophic heart, highlight CM heterogeneity, and provide a wealth of insights into molecular events involved in HCM that can eventually contribute to the development of enhanced therapies.
