医学新知2026，Vol.36Issue(4)：438-447,中插12,11.DOI:10.12173/j.issn.1004-5511.202510018
单核转录组学揭示心肌病亚型特异性细胞和分子特征
Single-nucleus transcriptomics reveals subtypes-specific cellular and molecular features of cardiomyopathy
摘要
Abstract
Objective To clarify the subtype-specific molecular mechanisms of hypertrophic cardiomyopathy(HCM),dilated cardiomyopathy(DCM),and arrhythmogenic cardiomyopathy(ACM)in terms of cellular composition,transcriptional features,and intercellular interactions.Methods The single-nucleus RNA sequencing(snRNA-seq)data from publicly available human heart tissue samples were integrated.Among them,HCM,DCM,and non-heart failure control samples were obtained from the Single Cell Portal database,whereas ACM samples were obtained from the European Genome-phenome Archive database.Data quality control,batch correction,clustering and annotation,differential expression and pathway enrichment analyses,cell-cell communication analysis,and spatial transcriptomics validation were performed to systematically characterize the cellular composition and molecular features of different cardiomyopathy subtypes.Results At the cellular composition level,all three cardiomyopathy subtypes exhibited reduced cardiomyocytes along with increased fibroblasts and smooth muscle cells,with the most pronounced changes observed in DCM.Subtype-specific differences were also evident:endothelial cells were increased in HCM and DCM but decreased in ACM;pericytes were markedly reduced in HCM,whereas both pericytes and neuronal cells were increased in ACM.At the molecular pathway level,HCM showed activation of the PI3K-AKT-mTOR pathway;DCM exhibited enhanced angiogenesis signaling;and ACM displayed significantly upregulated oxidative phosphorylation.Regarding key cellular subpopulations,HCM was enriched for Endothelial_c0-PIK3R3 and Fibroblast_c0-POSTN subsets;DCM showed increases in Myeloid_c0-C20orf194 and Fibroblast_c0-POSTN;while ACM was characterized by elevated Cardiomyocyte_c2-CDIN1,and Pericyte_c1-LOC644135 subsets.Furthermore,the pathway activities of Endothelial_c0-PIK3R3 in HCM and Fibroblast_c0-POSTN in DCM were validated using spatial transcriptomics.Conclusion This study systematically delineates subtype-specific cellular compositions and molecular functional features of cardiomyopathies,providing novel single-nucleus transcriptomic evidence for understanding the pathological mechanisms of HCM,DCM and ACM,and laying a foundation for precision diagnosis and therapeutic strategies for cardiomyopathies.关键词
心肌病/肥厚型心肌病/扩张型心肌病/致心律失常型心肌病/单核RNA测序技术Key words
Cardiomyopathy/Hypertrophic cardiomyopathy/Dilated cardiomyopathy/Arrhythmogenic cardiomyopathy/Single-nucleus RNA sequencing分类
医药卫生引用本文复制引用
句英娇,姚静怡,张松,闵力..单核转录组学揭示心肌病亚型特异性细胞和分子特征[J].医学新知,2026,36(4):438-447,中插12,11.基金项目
首都医科大学附属北京友谊医院种子计划(YYZZ202346) （YYZZ202346）
