心房颤动患者人成纤维细胞的单细胞RNA序列的生物信息学分析  

Bioinformatics analysis of single-cell RNA-seq of atrial human fibroblasts with atrial fibrillation

作　　者：周科 向杰 张长江 张莉 ZHOU Ke;XIANG Jie;ZHANG Changjiang;ZHANG Li(Cardiology Department,Affiliated Minda Hospital of Hubei Minzu University,Enshi 445000,Hubei,China)

机构地区：[1]湖北民族大学附属民大医院心血管内科,湖北恩施445000

出　　处：《中国现代医生》2023年第9期1-6,30,共7页China Modern Doctor

基　　金：湖北民族大学省级重点实验室开放基金(OIRI9011A)。

摘　　要：目的 筛选心房颤动(atrial fibrillation,AF)促纤维化的关键基因及信号通路,探讨AF诱导的人心房成纤维细胞的促纤维化重塑的分子机制。方法 从公共基因数据库(gene expression omnibus,GEO)下载单细胞RNA序列表达谱GSE148506,通过主成分分析和T分布式随机邻接嵌入得到差异基因,利用SingleR软件包进行细胞类型注释和轨迹分析,使用Clusterprofiler软件包,对成纤维细胞的差异基因进行基因本体(geneontology,GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genome,KEGG)信号通路分析。利用在线STRING数据库和Cytoscape软件进行蛋白质相互作用网络和模块分析。利用插件CytoHubba筛选出关键基因。结果 共得到6个细胞类型注释群,包括成纤维细胞、脂肪细胞、内皮细胞、单核细胞、成纤维细胞、骨骼肌细胞。共鉴定出367个成纤维细胞差异基因,包括37个下调基因和330个上调基因。GO功能富集分析结果显示,成纤维细胞的差异基因生物过程主要富集于细胞外基质组织等;细胞组成主要富集于含胶原细胞外基质等;分子功能主要富集于细胞外基质结构成分等。KEGG信号通路分析表明,差异基因主要富集于黏着斑、细胞外基质-受体相互作用等。STRING分析从蛋白质网络互作图中鉴定出6个成纤维细胞关键基因,即FN1、TIMP1、LAMB1、FBN1、C3、VCAN。结论 利用生物信息学分析,鉴定出FN1、TIMP1、LAMB1、FBN1、C3、VCAN在内的基因及黏着斑、细胞外基质-受体相互作用、磷脂酰肌醇3激酶-蛋白酶信号通路和转化生长因子-β信号通路可能是AF诱导的人心房成纤维细胞促纤维化重塑的重要分子机制。Objective To screen key genes and signaling pathways for pro-fibrosis in atrial fibrillation(AF) and explore the molecular mechanisms of AF-induced pro-fibrotic remodeling in human atrial fibroblasts.Methods Single-cell RNA-seq(scRNA-seq) expression profile GSE148506(AF and SR fibroblasts),was downloaded from the gene expression omnibus(GEO)database.The marker genes were obtained by quality control and data filtering,principal component analysis and t-distributed stochastic neighbor embedding.Single R package was utilized for cell type annotation and trajectory analysis.By using the Clusterprofiler package,the marker genes of fibroblasts were performed through gene ontology(GO) and Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis.Protein-protein interaction network analysis and module analysis was performed using the STRING database and Cytoscape software.The Hub genes were screened out by utilizing the plug-in cytoHubba.Results 6 clusters of cell type annotations were obtained,included fibroblasts,adipocytes,endothelialcells,monocytes,fibroblasts,skeletal muscle.A total of 367 fibroblasts marker genes were identified,included 37 down-regulated and 330up-regulated genes.GO functional enrichment analysis results showed that the marker genes for fibroblasts were predominantly enriched for extracellular matrix organization for biological process;collagen-containing extracellular matrix for cellular component;and extracellular matrix structural constituent for molecular function.KEGG pathway analyses indicated that the marker genes were meaningfully enriched in Focal adhesion,extracellular matrix(ECM)-receptor interaction,and so on.Top 6Hub genes of fibroblasts included FN1,TIMP1,LAMB1,FBN1,C3,VCAN.Conclusion Using bioinformatics analysis,we identified genes including FN1,TIMP1,LAMB1,FBN1,C3 and VCAN and Focal adhesion,ECM-receptor interactions,PI3K-AKT signaling pathway and transforming growth factor-β signaling pathway as possible important molecular mechanisms of pro-fibrotic remodeling in human atr

关 键 词：心房颤动 单细胞RNA序列 人心房成纤维细胞 生物信息学分析 

分 类 号：R541.7[医药卫生—心血管疾病]