Comprehensive analysis of scRNA-seq and bulk RNA-seq reveals the non-cardiomyocytes heterogeneity and novel cell populations in dilated cardiomyopathy

作者：Siyu He, Chunyu Li, Mingxin Lu, Lin Fang, Sangyu Hu, Junfang Zhang, Luying Peng, Li Li · 发表于：Journal of Translational Medicine · 年份：2025 · DOI：10.1186/s12967-024-05983-1 · 被引用次数：22 · 研究领域：Cardiac Fibrosis and Remodeling、Single-cell and spatial transcriptomics、Congenital heart defects research

BACKGROUND: Dilated cardiomyopathy (DCM) is one of the most common causes of heart failure. Infiltration and alterations in non-cardiomyocytes of the human heart involve crucially in the occurrence of DCM and associated immunotherapeutic approaches. METHODS: We constructed a single-cell transcriptional atlas of DCM and normal patients. Then, the xCell algorithm, EPIC algorithm, MCP counter algorithm, and CIBERSORT method were applied to identify DCM-related cell types with a high degree of precision and specificity using RNA-seq datasets. We further analyzed the heterogeneity among cell types, performed trajectory analysis, examined transcription factor regulatory networks, investigated metabolic heterogeneity, and conducted intercellular communication analysis. Finally, we used bulk RNA-seq data to confirm the roles of M2-like2 subpopulations and GAS6 in DCM. RESULTS: We integrated and analyzed Single-cell sequencing (scRNA-seq) data from 7 DCM samples and 3 normal heart tissue samples, totaling 70,958 single-cell data points. Based on gene-specific expression and prior marker genes, we identified 9 distinct subtypes, including fibroblasts, endothelial cells, myeloid cells, pericytes, T/NK cells, smooth muscle cells, neuronal cells, B cells, and cardiomyocytes. Using machine learning methods to quantify bulk RNA-seq data, we found significant differences in fibroblasts, T cells, and macrophages between DCM and normal samples. Further analysis revealed high heterogeneity in t...