■扩张型心肌病(DCM)是心力衰竭的第二大原因,具有复杂的病理生理基础。为了给DCM的机理研究提供新的启示,我们结合了大量RNA-seq和单细胞RNA-seq(scRNA-seq)数据,以检查与疾病有关的重要细胞和基因.
■该分析采用公开可获得的批量RNA-seq和scRNA-seqDCM数据集。scRNA-seq数据进行了归一化,主成分,和t分布随机邻居嵌入分析。使用CellChat进行细胞间通信网络和活动分析。利用富集分析,评估了标记基因在活性细胞中的作用。经过limma软件和加权基因共表达网络分析的筛选,差异表达基因(DEGs)作为hub基因。此外,这些hub基因进行了免疫学研究,转录因子表达,和基因集富集。最后,使用大鼠模型验证了4个hub基因的表达及其与DCM的联系.
■从八个鉴定的细胞簇中选择成纤维细胞和单核细胞作为hub细胞;它们的标记基因与DEGs相交以产生六个hub基因。此外,六个中心基因和必需模块基因相交产生四个必需基因(ASPN,SFRP4、LUM、和FRZB)连接到Wnt信号通路并在成纤维细胞中高表达。4个hubDEGs在DCM大鼠模型实验中的表达模式与生物信息学研究结果一致。此外,心功能下降与ASPN上调有很强的相关性,SFRP4、LUM、FRZB。
■最终,大量RNA-seq和scRNA-seq数据将成纤维细胞和单核细胞鉴定为涉及DCM的主要细胞类型。高表达的ASPN基因,FRZB,LUM,和SFRP4在成纤维细胞中可能有助于DCM的机制研究。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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 (ASPN, SFRP4, LUM, and FRZB) 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 ASPN, SFRP4, LUM, and FRZB.
UNASSIGNED: Ultimately, bulk RNA-seq and scRNA-seq data identified fibroblasts and monocytes as the main cell types implicated in DCM. The highly expressed genes ASPN, FRZB, LUM, and SFRP4 in fibroblasts may aid in the mechanistic investigation of DCM.