基于生物信息学探索小鼠ISL1调控心血管发育的作用
Exploration of the Regulatory Role of ISL1 in Cardiovascular Development in Mice Based on Bioinformatics
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摘要: 通过生物信息学的方法分析小鼠(Mus musculus)胰岛素增强子结合蛋白1(insulin enhancer binding protein 1,ISL1)基因表达缺失组和野生型组(对照组)在心血管发育过程中的差异表达基因(differentially expressed genes, DEGs),探索与ISL1表达缺失相关的下游基因靶点,揭示ISL1转录调控心血管发育的机制。从GEO数据库下载GSE80383和GSE65658的测序结果,利用生物信息学方法筛选出ISL1表达缺失组和对照组之间的DEGs(P<0.05,|log2FC|≥2)。用DAVID及STRING在线分析软件对DEGs分别进行功能富集分析和蛋白质-蛋白质相互作用(protein-protein interaction, PPI)网络分析。结果发现,ISL1在小鼠胚龄8.75天(embryonic day 8.75,E8.75)时的表达缺失主要调控近端/远端模式的形成,从而介导心血管发育;ISL1在小鼠胚龄10.5天(embryonic day 10.5,E10.5)时的表达缺失主要调控细胞增殖、细胞分化和多细胞生物的发育等生物过程;ISL1介导多种窦房结相关的基因调控窦房结细胞的发育。本研究探讨了小鼠ISL1在心血管发育中的作用,并分析了其可能的转录调控网络,从而为心血管疾病的分子基础和心脏再生提供理论基础。Abstract: The differentially expressed genes(DEGs) in the insulin enhancer binding protein 1(ISL1) gene deletion group and the wild-type group(control group) during cardiovascular development were analyzed in mice(Mus musculus) by bioinformatics to explore the downstream target genes associated with ISL1 expression deficiency and toelucidate the mechanism of ISL1 transcriptional regulation of cardiovascular development. The sequencing results of GSE80383 and GSE65658 were downloaded from the GEO database, and the DEGs between the ISL1 expression deletion group and the control group were screened by bioinformatics analysis(P<0.05, |log2FC|≥2). DAVID and STRING online analysis software were used for function enrichment analysis and protein-protein interaction(PPI) analysis of DEGs, respectively. The results showed that ISL1 expression deficiency in mice embryonic day 8.75(E8.75) mainly regulated proximal/distal pattern formation mediating cardiovascular development. ISL1 expression deficiency in mice embryonic day 10.5(E10.5) mainly regulated biological processes such as cell proliferation, differentiation and multicellular organisms, and ISL1 mediated multiple sinoatrial node-associated genes regulating sinoatrial node cell development. The research summarized the role of murine ISL1 in cardiovascular development and outlined its possible transcriptional regulatory network, thus providing a theoretical basis for the molecular basis of cardiovascular disease and cardiac regeneration.
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