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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
徐庶钦1,2,刘 龙1,2,李瑞芳3,韩岳兵1,2,刘智俊4
1.西安交通大学第一附属医院肝胆外科,西安 710000;2.西安交通大学第一附属医院精准外科与再生医学国家地方联合工程研究中心,西安 710061;3.内蒙古自治区乌兰察布市凉城县麦胡图镇综合保障和技术推广中心,乌兰察布 013750;4.西安交通大学第一附属医院感染性疾病科,西安 710000
摘要:
[摘要] 目的 探讨心肌梗死(MI)和脑卒中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,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GSE66360(MI)数据集和GSE16561(脑卒中)数据集,利用limma包进行差异表达分析,并绘制火山图。通过韦恩图分析筛选共同DEGs。利用clusterProfiler进行富集分析。进一步选取与心血管疾病密切相关通路上的关键DEGs,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大脑中动脉闭塞(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。结果 在GSE66360数据集和GSE16561数据集中,分别检测到1 785个 DEGs、561个DEGs,最终获得186个共同DEGs。富集分析发现肿瘤坏死因子产生的正向调节及中性粒细胞胞外诱捕网形成通路与心血管疾病密切相关。相关性分析显示,上述两个通路的DEGs与部分细胞死亡基因具有显著相关性。单细胞转录组分析结果显示,小鼠脑卒中模型组焦亡信号主要富集于单核细胞和小胶质细胞群中,其表达水平明显高于对照组。结论 MI与脑卒中共同的DEGs与焦亡通路核心因子呈显著相关,焦亡相关信号主要富集于单核细胞和小胶质细胞群。
关键词:  心肌梗死  脑卒中  差异表达基因  细胞死亡  富集分析
DOI:10.3969/j.issn.1674-3806.2026.04.07
分类号:
基金项目:陕西省自然科学基础研究计划项目(编号:2024JC-YBMS-692)
Analysis on the correlation of differentially expressed genes related to cardiovascular and cerebrovascular diseases with cell death-related genes
XU Shuqin1,2, LIU Long1,2, LI Ruifang3, HAN Yuebing1,2, LIU Zhijun4
1.Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi′an Jiaotong University, Xi′an 710000, China; 2.National Local Joint Engineering Research Center for Precision Surgery & Regenerative Medicine, the First Affiliated Hospital of Xi′an Jiaotong University, Xi′an 710061, China; 3.Comprehensive Support and Technology Promotion Center, People′s Government of Maihutu Town, Liangcheng County, Ulanqab City, Inner Mongolia Autonomous Region, Ulanqab 013750, China; 4.Department of Infectious Diseases, the First Affiliated Hospital of Xi′an Jiaotong University, Xi′an 710000, China
Abstract:
[Abstract] Objective To explore the shared characteristics of differentially expressed genes(DEGs) in the two disease models of myocardial infarction(MI) and stroke, and to analyze the cell-type specific distribution of cell death pathways by combining single-cell transcriptomic data, thereby revealing the potential association of cardiovascular and cerebrovascular diseases with mechanisms of programmed cell death. Methods The GSE66360(MI) and GSE16561(stroke) datasets were downloaded from Gene Expression Omnibus(GEO) database. DEGs analysis was conducted using the limma software package, and the volcano plots were generated. Venn diagram analysis was performed to screen the common DEGs of the two datasets. Enrichment analysis was performed by using clusterProfiler. The key DEGs in the pathways closely related to cardiovascular diseases were further selected, and their correlations with cell death-related gene set were analyzed, and scatter plots were generated. The single-cell transcriptomics data(GSE174574) of the middle cerebral artery occlusion(MCAO) mouse model of stroke were further used to analyze the expression patterns and enrichment characteristics of pyroptosis-related genes in different cell populations. Results In the GSE66360 and GSE16561 datasets, 1 785 and 561 DEGs were detected, respectively, and ultimately 186 shared DEGs were obtained. Enrichment analysis revealed that the positive regulation of tumor necrosis factors and the pathways of neutrophil extracellular traps(NETs) were closely related to cardiovascular diseases. Correlation analysis showed that the DEGs in the above two pathways were significantly correlated with some cell death genes. The results of single-cell transcriptomics analysis showed that the pyroptosis signals in the stroke mouse model group were mainly enriched in monocytes and microglial cells, and their expression levels were significantly higher than those in the control group. Conclusion The common DEGs shared by MI and stroke are significantly correlated with the core factors of pyroptosis pathways, and the pyroptosis-related signals are mainly enriched in monocytes and microglial cells.
Key words:  Myocardial infarction(MI)  Stroke  Differentially expressed genes(DEGs)  Cell death  Enrichment analysis