Huang Xiaoyan, Zhao Xiangrong, Li Yaping, Feng Yangmeng, Zhang Guoan, Wang Qiyu, Xu Cuixiang
Shaanxi Provincial Key Laboratory of Infection and Immune Diseases, Shaanxi Provincial People's Hospital, Xi'an, People's Republic of China.
Shaanxi Engineering Research Center of Cell Immunology, Shaanxi Provincial People's Hospital, Xi'an, People's Republic of China.
J Inflamm Res. 2024 Aug 14;17:5375-5388. doi: 10.2147/JIR.S470860. eCollection 2024.
Dilated cardiomyopathy (DCM) is the second leading cause of heart failure, with intricate pathophysiological underpinnings. In order to shed fresh light on the mechanistic research of DCM, we combined bulk RNA-seq and single-cell RNA-seq (scRNA-seq) data to examine significant cells and genes implicated in the disease.
This analysis employed publicly accessible bulk RNA-seq and scRNA-seq DCM datasets. The scRNA-seq data underwent normalization, principal component, and t-distribution stochastic neighbor embedding analysis. Cell-to-cell communication networks and activity analysis were conducted using CellChat. Utilizing enrichment analysis, the marker genes' role in the active cells was evaluated. After screening by limma software and weighted gene co-expression network analysis, the differentially expressed genes (DEGs) served as hub genes. Furthermore, these hub genes were subjected to immunological studies, transcription factor expression, and gene set enrichment. Lastly, the expression of the four hub genes and their connection to DCM were verified using the rat models.
Fibroblasts and monocytes were chosen as hub cells from among the eight identified cell clusters; their marker genes intersected with DEGs to yield six hub genes. In addition, the six hub genes and the essential module genes intersected to yield four essential genes (, and that were connected to the Wnt signaling pathway and highly expressed in fibroblast. The four hub DEGs had an expression pattern in the DCM rat model experiment results that was in line with the findings of the bioinformatics study. Additionally, there was a strong correlation between decreased cardiac function and the up-regulation of , and .
Ultimately, bulk RNA-seq and scRNA-seq data identified fibroblasts and monocytes as the main cell types implicated in DCM. The highly expressed genes , , and in fibroblasts may aid in the mechanistic investigation of DCM.
扩张型心肌病（DCM）是心力衰竭的第二大主要病因，其病理生理基础错综复杂。为了为DCM的机制研究提供新的线索，我们结合了批量RNA测序和单细胞RNA测序（scRNA-seq）数据，以研究与该疾病相关的重要细胞和基因。
本分析使用了可公开获取的批量RNA测序和scRNA-seq DCM数据集。对scRNA-seq数据进行了标准化、主成分分析和t分布随机邻域嵌入分析。使用CellChat进行细胞间通信网络和活性分析。利用富集分析评估标记基因在活性细胞中的作用。通过limma软件筛选和加权基因共表达网络分析后，差异表达基因（DEG）用作枢纽基因。此外，对这些枢纽基因进行了免疫学研究、转录因子表达和基因集富集分析。最后，使用大鼠模型验证了四个枢纽基因的表达及其与DCM的关联。
从八个鉴定出的细胞簇中选择成纤维细胞和单核细胞作为枢纽细胞；它们的标记基因与DEG相交，产生了六个枢纽基因。此外，六个枢纽基因与关键模块基因相交，产生了四个关键基因（ 以及 ），这些基因与Wnt信号通路相关，并在成纤维细胞中高表达。四个枢纽DEG在DCM大鼠模型实验结果中的表达模式与生物信息学研究结果一致。此外，心脏功能下降与 、 和 的上调之间存在很强的相关性。
最终，批量RNA测序和scRNA-seq数据确定成纤维细胞和单核细胞是与DCM相关的主要细胞类型。成纤维细胞中高表达的基因 、 和 可能有助于DCM的机制研究。
