Related Experiment Video
Updated: Jun 13, 2026
Isolation of Macrophage Subsets and Stromal Cells from Human and Mouse Myocardial Specimens
Published on: December 17, 2019
Integrative Transcriptomics and Machine Learning Identify Macrophage-Associated Biomarkers in Hypertrophic
Jianzhi Zhao1, Ximiao Su1, Jiali Wu1
1Departments of Cardiology, Central Laboratory, The First Affiliated Hospital of Harbin Medical University, Harbin 150010, China.
Insights
Hypertrophic cardiomyopathy (HCM) involves macrophage dysfunction. This study identifies key genes like F13A1 in macrophages, revealing reduced immune cell interactions and offering potential diagnostic markers for this common genetic heart disease.
Area of Science:
- Cardiovascular Biology
- Immunology
- Genetics
Background:
- Hypertrophic cardiomyopathy (HCM) is a prevalent genetic heart condition.
- Macrophages are integral to the pathological remodeling observed in HCM.
Purpose of the Study:
- To elucidate the molecular underpinnings of HCM by examining macrophage gene expression at a single-cell resolution.
- To identify novel diagnostic biomarkers and understand cellular communication alterations in HCM.
Main Methods:
- Analysis of published single-cell RNA sequencing (scRNA-seq) datasets (GSE181764, GSE161921) and bulk RNA-seq data (GSE249925).
- Identification of key cell clusters and hub genes through differential expression and immune infiltration analyses.
- Intercellular communication analysis and single-cell validation of gene expression.
Main Results:
- Macrophages were identified as a key cell cluster associated with HCM.
- Three hub genes (ASPN, F13A1, SORBS2) were identified, with F13A1 showing high macrophage specificity and downregulation in HCM.
- HCM patients exhibited decreased immune cell subsets and significantly reduced intercellular communication, particularly affecting macrophage signaling.
Conclusions:
- Macrophage dysfunction and altered intercellular communication are critical in HCM pathogenesis.
- F13A1 serves as a potential diagnostic marker for HCM.
- A LASSO-based diagnostic model incorporating IGFBP4, FOS, and CTSC demonstrates high predictive accuracy for HCM.
Abstract:
Hypertrophic cardiomyopathy (HCM) is a common genetic heart disease, with macrophages playing a critical role in its pathological remodeling. Our study aims to investigate the molecular basis of HCM by analyzing macrophage-related gene expression at the single-cell level. Utilizing published scRNA-seq datasets (GSE181764 and GSE161921), we identified macrophages as the key cell cluster most associated with HCM. Integration with bulk RNA-seq data (GSE249925) and differential expression analysis revealed three hub genes: ASPN (asporin), F13A1 (Coagulation Factor XIII A Chain), and SORBS2 (Sorbin and SH3 domain-containing protein 2). Immune infiltration analysis showed significant decreases in multiple immune cell subsets in HCM patients, including neutrophil and macrophages. Intercellular communication analysis revealed an approximately 50% reduction in total interactions in HCM, accompanied by markedly weakened macrophage signaling reception and loss of regulatory pathways. Single-cell validation confirmed that F13A1 expression was predominantly restricted to macrophage clusters and significantly downregulated in HCM macrophages, demonstrating strong macrophage specificity and diagnostic potential. Furthermore, a LASSO-based diagnostic model incorporating three genes (IGFBP4, FOS, CTSC) exhibited high predictive performance, with validated accuracy in both training and external validation sets. Collectively, our findings shed light on the mechanisms underlying macrophage dysfunction in HCM and offer novel insights into the cellular and molecular dynamics.
