Identification of Ferroptosis- and Hypoxia-related Genes in iPSC-derived Oligodendrocyte Precursor Cells from Multiple Sclerosis Patients.

IF 1.2 4区 综合性期刊 Q3 MULTIDISCIPLINARY SCIENCES
Xia Zhang, Yuming Wang, Ruifang Sui, Yong Zhong, Ping Yi
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引用次数: 0

Abstract

Multiple sclerosis (MS) is a chronic inflammatory disorder characterized by demyelination, with failed remyelination leading to progressive axon loss in chronic stages. Oligodendrocyte precursor cells (OPCs) are critical for remyelination. Recent studies suggest that both hypoxia and ferroptosis play crucial roles in the dysfunctional differentiation of OPCs. This research seeks to identify key genes linked to hypoxia and ferroptosis and immune infiltration characteristics in OPCs derived from induced pluripotent stem cells (iPSCs) of MS patients and to construct a diagnostic model centered on these pivotal genes. We analyzed gene expression data from the GSE196575 and GSE147315 datasets and compared MS patients with healthy individuals. Using weighted gene coexpression network analysis (WGCNA), we pinpointed primary module genes and essential genes associated with hypoxia, ferroptosis, and MS. The ferroptosis Z score and the hypoxia Z score calculated via gene set variation analysis (GSVA) were greater in the iPSC-derived OPCs of MS patients than those of the control group. The implicated genes are predominantly linked to the PI3K/Akt/mTOR pathway, as identified through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. A protein-protein interaction (PPI) network of crucial genes revealed 10 central hub genes (COL4A1, COL4A2, ITGB5, ITGB1, ITGB8, ITGAV, VIM, FLNA, VCL, and SPARC). The robust expression of ITGB1, ITGB8, and VIM was validated in the GSE151306 dataset, supporting their role as key hub genes. Additionally, an interaction network between transcription factors (TFs) and hub genes was established via Transcriptional Regulatory Relationships Unraveled by Sentence-based Text (TRRUST), which identified five key TFs. The results of this study could help elucidatenovel biomarkers or therapeutic targets for MS.

多发性硬化症(MS)是一种慢性炎症性疾病,其特点是脱髓鞘,再髓鞘化失败会导致慢性期轴突进行性丧失。少突胶质细胞前体细胞(OPCs)是再髓鞘化的关键。最近的研究表明,缺氧和铁变态反应在 OPCs 的功能性分化障碍中起着至关重要的作用。本研究旨在确定与缺氧和铁中毒以及多发性硬化症患者诱导多能干细胞(iPSCs)衍生的OPCs免疫浸润特征相关的关键基因,并以这些关键基因为中心构建诊断模型。我们分析了来自 GSE196575 和 GSE147315 数据集的基因表达数据,并将多发性硬化症患者与健康人进行了比较。通过加权基因共表达网络分析(WGCNA),我们确定了与缺氧、铁变性和多发性硬化症相关的主要模块基因和重要基因。与对照组相比,通过基因组变异分析(GSVA)计算出的多发性硬化症患者 iPSC 衍生的 OPCs 中的铁突变 Z score 和缺氧 Z score 更大。通过基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析发现,受影响的基因主要与PI3K/Akt/mTOR通路有关。关键基因的蛋白-蛋白相互作用(PPI)网络揭示了10个中心枢纽基因(COL4A1、COL4A2、ITGB5、ITGB1、ITGB8、ITGAV、VIM、FLNA、VCL和SPARC)。ITGB1、ITGB8和VIM的强表达在GSE151306数据集中得到了验证,支持了它们作为关键枢纽基因的作用。此外,通过基于句子的文本转录调控关系揭示(TRRUST)建立了转录因子(TFs)与枢纽基因之间的相互作用网络,确定了五个关键TFs。这项研究的结果有助于阐明多发性硬化症的新型生物标志物或治疗靶点。
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来源期刊
Jove-Journal of Visualized Experiments
Jove-Journal of Visualized Experiments MULTIDISCIPLINARY SCIENCES-
CiteScore
2.10
自引率
0.00%
发文量
992
期刊介绍: JoVE, the Journal of Visualized Experiments, is the world''s first peer reviewed scientific video journal. Established in 2006, JoVE is devoted to publishing scientific research in a visual format to help researchers overcome two of the biggest challenges facing the scientific research community today; poor reproducibility and the time and labor intensive nature of learning new experimental techniques.
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