非梗阻性无精子症支持细胞铁代谢相关差异表达基因的生物信息学分析  

Bioinformatics analysis of differentially expressed genes related to iron metabolism in sertoli cells of non obstructive azoospermia

作　　者：杜昭霞 张畅 王学芹 DU Zhaoxia;ZHANG Chang;WANG Xueqin(Department of Reproductive Medicine,Qingdao Municipal Hospital,Qingdao,Shandong 266000,China)

机构地区：[1]青岛市市立医院生殖医学科,山东青岛266000

出　　处：《中国优生与遗传杂志》2024年第12期2558-2563,共6页Chinese Journal of Birth Health & Heredity

摘　　要：目的通过生物信息学方法分析非梗阻性无精子症(NOA)男性睾丸支持细胞中的铁代谢相关差异表达基因。方法从GEO数据库中获取GSE149512数据集,选取无生精障碍的人群和NOA患者为研究对象。数据集的过滤、质控、标准化及其降维处理均运用R软件中的Seurat包;细胞聚类分析使用非线性降维UMAP方法;使用原文献提供的Marker对细胞类型进行注释;使用Findermarker函数计算支持细胞在NOA组与正常组间的差异表达基因;使用R包clusterProfiler对差异基因进行GO和KEGG功能富集;从GO数据库和FerrDb V2数据库获取铁代谢相关基因,并与差异表达基因取交集绘制维恩图,构建差异表达基因的蛋白-蛋白互作(PPI)网络图。结果分析两组研究对象睾丸支持细胞共得到244个差异表达基因,与正常组相比,NOA组192个基因下调、52个基因上调。铁代谢相关的差异表达基因有13个:TF、TMSB4X、GPX4、EGR1、ZFP36、TFAM、TNFAIP3、NR4A1、AQP5、NUPR1、ATF3、TTYH1、B2M。PPI网络结果显示,GPX4、GSS和B2M为核心基因。结论本研究通过生物信息学方法显示了NOA患者支持细胞中与铁代谢相关的差异表达基因,为后续探讨NOA的新机制奠定了基础。Objective To analyze differentially expressed genes related to iron metabolism in testicular sertoli cells of non-obstructive azoospermia(NOA)by bioinformatics methods.Methods The GSE149512 dataset was obtained from the GEO database,and the population without spermatogenic disorders and NOA patients were selected as the research subjects.Seurat package in R software was used to filter,quality control,standardize,and reduce dimensions of the dataset.Non-linear dimensionality reduction UMAP method was used for cell clustering analysis.The markers provided in the original literature to annotate cell types were used in our study.Findermarker function was used to calculate the differentially expressed genes of sertoli cells between the NOA group and the normal group.GO and KEGG functional enrichment on differentially expressed genes were used by the R package clusterProfiler.Intersection of iron metabolism related genes obtained from GO database and FerrDb V2 database and differentially expressed genes to draw a Venn diagram,and construct a protein-protein interaction(PPI)network diagram of differentially expressed genes.Results A total of 244 differentially expressed genes were identified in the testicular sertoli cells of the two studied groups.Compared with the normal group,the NOA group showed 192 downregulation genes and 52 upregulation genes.There were 13 differentially expressed genes related to iron metabolism:TF,TMSB4X,GPX4,EGR1,ZFP36,TFAM,TNFAIP3,NR4A1,AQP5,NUPR1,ATF3,TTYH1 and B2M.The PPI network results show that GPX4,GSS,and B2M were hub genes.Conclusion Differentially expressed genes related to iron metabolism in sertoli cells of NOA patients were found in this study by bioinformatics methods,laying the foundation for exploring new mechanisms of NOA in the future.

关 键 词：单细胞测序 睾丸支持细胞 非梗阻性无精子症 铁代谢 

分 类 号：R69[医药卫生—泌尿科学]