人类精原细胞分化过程的生物信息学分析

Bioinformatics analysis of human spermatogonia differentiation process

目的为了明确精子发生过程中的关键基因和生物学过程, 挖掘人类精原细胞(spermatogonia, SPG)分化过程中的差异表达基因(differentially expressed genes, DEGs)及其信号通路, 探索精子发生早期的分子机制, 增加对SPG分化过程的分子生物学认识。方法从公共数据库下载人类未分化精原细胞(undifferentiated spermatogonia, uSPG)和分化精原细胞(differentiating spermatogonia, dSPG)的转录组数据, 利用Hisat2和StingTie筛选DEGs, 并对差异表达基因进行GO和KEGG功能富集分析。利用MACS2软件对ATAC-seq数据中开放染色质区域进行富集分析。结果共筛选出8 532个DEGs, 包括4 127个上调基因和4 405个下调基因, 它们通过一些重要的生物学过程, 如细胞周期、细胞因子介导的信号通路、有机物代谢过程、细胞运动、甲基化等来调控SPG的分化过程。KEGG富集分析结果表明一些重要信号通路包括FoxO信号通路、JAK-STAT信号通路等在SPG分化过程中具有重要作用。GO富集分析结果显示甲基化在SPG分化过程中发挥重要作用, 甲基化相关基因表达差异显著。组蛋白甲基化词条相关基因TDRDs家族显著富集, 9个TDRDs基因在dSPG中表达更加活跃。结论本研究通过生物信息学分析鉴定了SPG分化过程中的差异表达基因, 明确了关键基因在转录和染色质水平的差异, 为SPG分化机制研究奠定了重要的理论基础。

Objective To clarify the key genes and biological processes in spermatogenesis,integrate and analyze the differentially expressed genes(DEGs)and key signaling pathways in the differentiation process of human spermatogonia(SPG),and to explore the early molecular mechanism of spermatogenesis,increase the molecular biology understanding of SPG differentiation process.Methods The transcriptome data of human undifferentiated spermatogonia and differentiated spermatogonia(dSPG)were downloaded from the public database.Hisat2 and StingTie were used to screen DEGs.DEGs were analyzed by gene ontology(GO)and Kyoto encyclopedia of genes and genomes(KEGG)functional enrichment analysis.MACS2 software was used to analyze the open chromatin regions(OCRs)in ATAC-seq data.Results A total of 8532 DEGs were screened,including 4127 up-regulated genes and 4405 down-regulated genes.They regulate the differentiation of SPG through some important biological processes,such as cell cycle,cytokine-mediated signaling pathways,organic matter metabolism,cell movement,and methylation.KEGG enrichment analysis showed that some important signaling pathways including FoxO signaling pathway and JAK-STAT signaling pathway played an important role in SPG differentiation.GO enrichment analysis showed that methylation played an important role in the differentiation of SPG,and the expression of methylation-related genes was significantly different.The TDRDs family was significantly enriched,and 9 TDRDs genes were found to be more active in dSPG.Conclusion In this study,the differentially expressed genes during SPG differentiation were identified by bioinformatics analysis,and the differences in transcription and chromatin levels of key genes were clarified,which laid an important theoretical foundation for the study of SPG differentiation mechanism.