Integration single-cell and bulk RNA-sequencing data to reveal senescence gene expression profiles in heart failure

Abstract

BackgroundHeart failure (HF) represents one of healthcare's biggest challenges. Although rarely noticed, aging is a crucial risk factor for cardiovascular disease. Our study aims to reveal aging's role in HF by integrating single-cell RNA-sequencing (scRNA-seq) and bulk RNA-sequencing databases. MethodsWe collected HF heart sample data from the Gene Expression Omnibus database and senescence gene data from CellAge. The FindCluster () package was used for cell cluster analysis. Differentially expressed genes (DEG) were identified operating the FindMarkers function. Cell activity score calculation was performed using the AUCell package. UpSetR plotted the intersection between DEGs of active cell types, bulk data DEGs, and genes associated with aging. Using the DGIdb database gene-drug interaction data, we search for potential targeted therapeutics based on common senescence genes. ResultsThe scRNA-seq data revealed myocardial heterogeneity in HF tissues. A series of crucial common senescence genes were found. The senescence gene expression profile hints at an intriguing connection between monocytes and HF. After analyzing the DEGs in the bulk dataset, the DEGs in scRNA-seq, the DEGs in each active cell type, and senescence genes, we identified ten genes as common senescence genes present in HF. Correlation analysis of transcriptomics, proteomics, and ceRNA was performed to provide ideas for future studies individually. Moreover, we discovered that common senescence genes and potential therapeutic drugs interact among different cell types. Further research is needed on the expression pattern of senescence genes and molecular regulation in HF. ConclusionsIn summary, we identified the functional significance of the senescence gene in HF using integrated data. It is possible that this more profound understanding of how senescence contributes to the development of HF will aid in unraveling the mechanisms that promote the disease and provide hints for developing therapeutics.