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Identification and Verification of Candidate Genes Regulating Neural Stem Cells Behavior Under Hypoxia

机译:缺氧条件下调节神经干细胞行为的候选基因的鉴定与验证

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Background/Aims Neural stem cells (NSCs) reside in a hypoxic environment, and hypoxia plays an important role in their development and differentiation. This study aimed to explore the underlying mechanisms by which hypoxia affects NSC behavior. Methods In the current study, we downloaded the gene expression dataset GSE68572 and identified the differentially expressed genes (DEGs) by analyzing high-throughput gene expression in hypoxic and normoxic NSCs. Subsequently, we analyzed these data using a combined bioinformatics approach and predicted the microRNAs (miRNAs) targeting the key gene using miRNA databases. Quantitative real-time PCR (qRT-PCR) was used to validate the expression of the top five DEGs. Results In total, 1347 genes were identified as DEGs. We identified the predominant gene ontology categories and Kyoto Encyclopedia of Genes and Genomes pathways that were significantly over-represented in the hypoxic NSCs. A protein–protein interaction network he identification of miRNAs and their putative targets may offer new diagnostic and therapeutic strategies for liver cancer the top 10 core genes. Vascular endothelial growth factor A (VEGFA) had the highest degree and may be the key gene concerning NSC behavior under hypoxia. Further validation of the top five DEGs by qRT-PCR demonstrated that four DEGs were significantly higher and one DEG was significantly lower in the hypoxic group than in the control group. Seven miRNAs were predicted and proved to target VEGFA. Conclusion This preliminary study can prompt the understanding of the molecular mechanisms by which hypoxia has an impact on NSC behavior and can help to optimize stem cell therapies for central nervous system injuries and diseases.
机译:背景/目的神经干细胞(NSC)处于低氧环境中,缺氧在其发育和分化中起重要作用。这项研究旨在探讨缺氧影响NSC行为的潜在机制。方法在本研究中,我们下载了基因表达数据集GSE68572,并通过分析缺氧和常氧NSC中的高通量基因表达来鉴定差异表达基因(DEG)。随后,我们使用组合的生物信息学方法分析了这些数据,并使用miRNA数据库预测了靶向关键基因的microRNA(miRNA)。实时定量PCR(qRT-PCR)用于验证前五个DEG的表达。结果共鉴定出1347个基因为DEG。我们确定了主要的基因本体论类别和《京都全书》的基因和基因组途径百科全书,在缺氧的NSC中明显过高。鉴定miRNA及其假定靶点的蛋白质-蛋白质相互作用网络可能为肝癌的前10个核心基因提供新的诊断和治疗策略。血管内皮生长因子A(VEGFA)的程度最高,可能是缺氧时NSC行为的关键基因。通过qRT-PCR对前五个DEG的进一步验证表明,低氧组的四个DEG显着高于对照组,一个DEG显着低于对照组。预测了七个miRNA,并证明它们靶向VEGFA。结论这项初步研究可以促进了解缺氧影响NSC行为的分子机制,并有助于优化用于中枢神经系统损伤和疾病的干细胞疗法。

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