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RNA Sequencing of CD4+ T Cells in Relapsing–Remitting Multiple Sclerosis Patients at Relapse: Deciphering the Involvement of Novel genes and Pathways
Journal of Molecular Neuroscience ( IF 2.8 ) Pub Date : 2021-07-21 , DOI: 10.1007/s12031-021-01878-8
Zahra Salehi 1 , Saeed Talebi 2, 3 , Samaneh Maleknia 4 , Fahimeh Palizban 5 , Abdorreza Naser Moghadasi 6 , Kaveh Kavousi 5 , Mohammad Ali Sahraian 6 , Maryam Izad 1, 6
Affiliation  

CD4+ T cells are known as a noteworthy potential modulator of inflammation in multiple sclerosis (MS). In the current study, we investigated the transcriptome profile of CD4+ T cells in patients with relapsing–remitting MS (RRMS) at the relapse phase. We performed RNA sequencing of CD4+ T cells isolated from four relapsing–remitting MS (RRMS) patients at the relapse phase and four age- and sex-matched healthy controls. The edgeR statistical method was employed to determine differentially expressed genes (DEGs). Gene set enrichment analysis was subsequently performed. Applying a physical interaction network, genes with higher degrees were selected as hub genes. A total of 1278 and 1034 genes were defined at significantly higher or lower levels, respectively, in CD4+ T cells of RRMS patients at the relapse phase as compared with healthy controls. The top up- and downregulated genes were JAML and KDM3A. The detected DEGs were remarkable on chromosomes 1 and 2, respectively. The DEGs were mainly enriched in the pathways “regulation of transcription, DNA-templated,” “regulation of B cell receptor signaling pathway,” “protein phosphorylation,” “epidermal growth factor receptor signaling pathway,” and “positive regulation of neurogenesis.” Moreover, 16 KEGG pathways mostly associated with the immune system and viral infections were enriched. In the constructed physical interaction networks, UBA52 and TP53 were shown to be the most highly ranked hub genes among upregulated and downregulated genes, respectively. By applying global transcriptome profiling of CD4+ T cells, we deciphered the involvement of several novel genes and pathways in MS pathogenesis. The present results must be confirmed by in vivo and in vitro studies.



中文翻译:

复发-缓解型多发性硬化症患者中 CD4+ T 细胞的 RNA 测序:破译新基因和通路的参与

CD4 + T 细胞被认为是多发性硬化症 (MS) 中值得注意的潜在炎症调节剂。在目前的研究中,我们调查了复发-缓解型 MS (RRMS) 患者在复发期的 CD4 + T 细胞转录组谱。我们对 CD4 +进行了 RNA 测序从四名处于复发期的复发缓解型 MS (RRMS) 患者和四名年龄和性别匹配的健康对照中分离出的 T 细胞。采用edgeR统计方法确定差异表达基因(DEGs)。随后进行基因集富集分析。应用物理交互网络,选择度数较高的基因作为枢纽基因。与健康对照组相比,在复发期 RRMS 患者的CD4 + T 细胞中,共有 1278 和 1034 个基因分别被定义为显着更高或更低的水平。上调和下调的基因是JAMLKDM3A。检测到的 DEG 分别在 1 号和 2 号染色体上显着。DEGs主要富集在“转录调控、DNA模板化”、“B细胞受体信号通路调控”、“蛋白质磷酸化”、“表皮生长因子受体信号通路”和“神经发生的正调控”等通路中。此外,还丰富了 16 条主要与免疫系统和病毒感染相关的 KEGG 途径。在构建的物理相互作用网络中,UBA52TP53分别被证明是上调和下调基因中排名最高的枢纽基因。通过应用 CD4 +的全局转录组分析T 细胞,我们破译了几个新基因和途径参与 MS 发病机制。目前的结果必须通过体内和体外研究来证实。

更新日期:2021-07-22
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