人诱导多能干细胞分化为心肌细胞关键基因的生物信息学分析

Bioinformatics Analysis of Key Genes Implicated in Differentiation of Human Induced Pluripotent Stem Cells to Cardiomyocytes

利用生物信息学分析的方法筛选人诱导多能干细胞(induced pluripotent stem cells,i PSCs)向心肌细胞分化的关键基因。收集GEO(Gene Expression Omnibus)数据库中关于人i PSCs向心肌细胞分化的高通量测序数据,包含i PSCs向心肌细胞分化的4个阶段的样本数据,分别是未分化的i PSCs(D0)、中胚层细胞(D2)、早期心肌细胞(D7)和心肌细胞(D14)。应用R包分析D0、D2、D7和D14样品之间的差异表达基因,并对差异表达基因进行功能和信号通路分析;构建差异表达基因的蛋白质-蛋白质互作(protein-protein interaction,PPI)网络;应用R包加权基因共表达网络分析(weighted gene co-expression network analysis,WGCNA)对共表达的基因进行聚类,并将其划分为不同的基因模块;使用Cytoscape软件对重要基因模块的互作网络进行可视化和富集分析。结果显示,D0、D2、D7和D14样品之间的差异表达基因总共达917个,基于PPI网络筛选到的前10个基因分别是FPR2、ADCY2、CXCR2、CXCR4、PF4、GALR1、GAL、CXCL5、CXCL6和HCAR3,其中FPR2、CXCR2、CXCR4、PF4都富集G蛋白偶联受体配体结合的通路。基因相互作用关系分析显示,BMP5处于调控心肌发育的核心地位。研究基于表达谱GSE137920数据的生物信息学分析,筛选到人i PSCs向心肌细胞分化的关键基因,这将有助于心肌分化发育分子机制的深入研究。

Bioinformatics analysis methods were used to screen the key genes involved in differentiation of cardiomyocytes from human induced pluripotent stem cells(iPSCs).The expression data of high-throughput sequencing of human iPSCs differentiation into cardiomyocytes were collected from the Gene Expression Omnibus(GEO)database,including sample data of 4 differentiation stages,namely undifferentiated iPSCs(D0),mesoderm cells(D2),early cardiomyocytes(D7),and cardiomyocytes(D14).The differentially expressed genes of D0,D2,D7,and D14 were analyzed by the R package,and their functions and signal pathways were analyzed.The protein-protein interaction(PPI)network of the differentially expressed genes was constructed.The coexpressed genes were clustered and divided into different gene modules by the R package weighted gene coexpression network analysis(WGCNA).The Cytoscape software was used for visualization and enrichment analysis of the interaction network in important gene module.A total of 917 differentially expressed genes were obtained in the D0,D2,D7 and D14 samples.The top 10 genes screened based on PPI network were FPR2,ADCY2,CXCR2,CXCR4,PF4,GALR1,GAL,CXCL5,CXCL6,and HCAR3,among which FPR2,CXCR2,CXCR4,and PF4 were all enriched in G-protein-coupled receptor-ligand binding.According to the interaction between genes in modules,BMP5 was found to be at the core of regulating myocardial development.Through bioinformatics analysis of the expression profile GSE137920,the key genes in differen-tiation of iPSCs into cardiomyocytes were screened out.The results may be helpful for in-depth research on the molecular mechanism of cardiac differentiation and development.