| 引用本文: | 徐庶钦,刘龙,李瑞芳,刘智俊.心脑血管疾病相关差异基因与细胞死亡基因的相关性分析[J].中国临床新医学,0,():-. |
| .心脑血管疾病相关差异基因与细胞死亡基因的相关性分析[J].中国临床新医学,0,():-. |
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| 摘要: |
| 目的 探讨心肌梗死（Myocardial Infarction, MI）和脑卒中（Stroke）两种疾病模型中差异表达基因（DEGs）的共有特征，并结合单细胞转录组数据分析细胞死亡通路的细胞特异性分布，从而揭示心脑血管疾病与程序性细胞死亡机制的潜在关联。 方法 从GEO数据库中下载心肌梗死（GSE66360）和脑卒中（GSE16561）数据集，利用limma包进行差异表达分析，并进行火山图绘制。对两组DEGs进行韦恩图分析筛选共有差异基因。随后利用clusterProfiler进行GO和KEGG功能富集分析。进一步选取GO:0032760通路与KEGG通路hsa04613通路的关键差异基因，与细胞死亡基因合集进行相关性分析，并绘制散点图。进一步利用脑卒中小鼠MCAO模型的单细胞转录组数据（GSE174574），分析焦亡相关基因在不同细胞群中的表达模式和富集特征，以验证bulk RNA-seq的发现。 结果 心肌梗死与脑卒中分别鉴定出显著的差异表达基因，通过韦恩图分析获得两种疾病共有的差异基因。功能富集分析发现GO:0032760及KEGG:hsa04613与疾病密切相关。相关性分析显示，上述两个通路的差异基因与部分细胞死亡基因具有明显相关性（相关系数R > 0.6），提示这些基因可能在疾病进展中通过细胞死亡通路发挥作用。单细胞转录组进一步揭示，在MCAO模型中，焦亡信号主要富集于单核细胞和微胶质细胞群中，其表达水平在MCAO组明显高于对照组，与bulk分析结果一致，提示免疫细胞是焦亡激活的关键执行群体。 结论 心肌梗死与脑卒中共享的差异表达基因主要参与TNF介导信号与NETs形成通路，这些基因与焦亡通路核心因子高度相关。单细胞分析进一步验证了焦亡信号在单核/微胶质细胞中的空间富集，揭示细胞死亡在心脑血管疾病病理过程中的关键免疫驱动作用，为精准靶向焦亡通路提供了新的理论依据。 |
| 关键词: 心肌梗死 脑卒中 差异基因 细胞死亡 功能富集分析 |
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| 基金项目:陕西省自然科学基础研究计划项目(编号：2024JC-YBMS-692) |
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| Correlation Analysis Between Differentially Expressed Genes Associated with Cardiovascular and Cerebrovascular Diseases and Cell Death-Related Genes |
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1.The First Affiliated Hospital of Xi'2.'3.an Jiaotong University;1.The First Affiliated Hospital of Xi'2.'3.an Jiaotong University
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| Abstract: |
| Objective: To explore the shared characteristics of differentially expressed genes (DEGs) between myocardial infarction (MI) and stroke, and to further integrate single-cell transcriptomic data to uncover the cell-type-specific distribution of cell death pathways, revealing the potential mechanisms linking cardiovascular and cerebrovascular diseases with programmed cell death.
Methods: Transcriptomic datasets for MI (GSE66360) and stroke (GSE16561) were retrieved from the Gene Expression Omnibus (GEO) database. Differential expression analysis was conducted using the limma package, and volcano plots were generated. Common DEGs were identified through Venn diagram analysis. Functional enrichment analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), was performed using the clusterProfiler package. DEGs enriched in GO term GO:0032760 (positive regulation of tumor necrosis factor production) and KEGG pathway hsa04613 (neutrophil extracellular trap formation) were selected for correlation analysis with a curated set of cell death-related genes. Scatter plots were generated to visualize the correlations. Additionally, single-cell transcriptomic data from a mouse MCAO model (GSE174574) were analyzed to determine the spatial and cellular distribution of pyroptosis-related genes and to validate bulk RNA-seq findings.
Results: A substantial number of DEGs were identified in both the MI and stroke datasets. Venn analysis revealed a subset of DEGs common to both conditions. GO and KEGG enrichment analyses highlighted GO:0032760 and KEGG:hsa04613 as key pathways implicated in disease mechanisms. Correlation analysis showed that several key genes within these pathways were strongly associated with cell death-related genes (Pearson’s R > 0.6), suggesting their potential involvement in disease progression via cell death mechanisms. Single-cell analysis revealed that pyroptosis signatures were predominantly enriched in monocytes and microglia in the MCAO model, with higher expression levels compared to controls, consistent with the bulk RNA-seq results.
Conclusion: The shared DEGs between MI and stroke are mainly involved in TNF signaling and NETs formation, showing significant correlations with pyroptosis pathway genes. |
| Key words: Myocardial infarction Stroke Differentially expressed genes Cell death Functional enrichment analysis |
