首页|T细胞参与慢性阻塞性肺疾病潜在机制的单细胞转录组生物信息学研究

T细胞参与慢性阻塞性肺疾病潜在机制的单细胞转录组生物信息学研究

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目的 利用单细胞转录组生物信息学方法探讨T细胞参与慢性阻塞性肺疾病发病的潜在机制。方法 从高通量基因表达数据库下载单细胞转录组数据集GSE173896,利用R语言的Seurat数据包对数据进行过滤和标准化;将具有相似特征基因的细胞进行聚类和注释,筛选与慢性阻塞性肺疾病发病相关的细胞亚群,提取T细胞亚群进行二次分析;利用R语言CellChat数据包分析T细胞与其他细胞亚群之间细胞通讯;筛选T细胞差异表达基因并进行富集分析,构建蛋白质互作网络筛选核心基因;下载GSE69818、GSE37768和GSE106986三个数据集,验证并筛选慢性阻塞性肺疾病发病的关键核心基因,绘制受试者操作特征曲线评价关键核心基因预测慢性阻塞性肺疾病发病的价值。结果 过滤获得慢性阻塞性肺疾病患者肺组织细胞9313个,健康对照者肺组织细胞11716个;慢性阻塞性肺疾病肺组织T细胞占比高,其中辅助性T细胞数量高于健康对照组,调节性T细胞数量少于健康对照组;T细胞与单核细胞、B细胞、内皮细胞和自然杀伤细胞等细胞的交互强度明显上调;筛选获得T细胞相关的差异表达上调基因46个,差异表达下调基因32个;差异表达基因显著富集于白细胞介素-17、肿瘤坏死因子-α、核转录因子Kappa B和Toll样受体等信号通路上。TIMP1、CXCL5是慢性阻塞性肺疾病发病的关键核心基因。结论 慢性阻塞性肺疾病与健康肺组织细胞分布存在较大差异,T细胞与慢性阻塞性肺疾病发病密切相关,是预防和治疗慢性阻塞性肺疾病的潜在靶细胞,慢性阻塞性肺疾病发病涉及多种炎性信号通路,TIMP1、CXCL5是慢性阻塞性肺疾病发病的关键核心基因。
Single-cell transcriptomic bioinformatics study of potential mechanisms of T cells involvement in chronic obstructive pulmonary disease
[Objective]To explore the potential mechanism of T cell involvement in the pathogenesis of chronic obstructive pulmonary disease (COPD) using single-cell transcriptome bioinformatics methods.[Methods]Single-cell transcriptome dataset GSE173896 was downloaded from the Gene Expression Omnibus database,the data were filtered and normalized using the Seurat package in R.Cells with similar characteristic genes were clustered and annotated to screen for cell subtypes associated with the development of COPD.T cell subtypes were extracted for secondary analysis.Cellchat package in R was used to analyze cell communication between T cells and other cell subtypes.Differential expression genes in T cells were screened and subjected to enrichment analysis to construct a protein interaction network to identify core genes.Three datasets (GSE69818,GSE37768,and GSE106986) were downloaded to verify and screen key core genes related to the development of COPD,and receiver operating characteristic (ROC) curves were plotted to evaluate the value of predicting the occurrence of COPD.[Results]A total of 9,313 lung tissue cells from patients with COPD and 11,716 lung tissue cells from healthy controls were filtered.T cells accounted for a higher proportion of lung tissue cells in patients with COPD,and the number of helper T cells was higher than that in the healthy control group,while the number of regulatory T cells was lower.The interaction intensity between T cells and monocytes,B cells,endothelial cells,and natural killer cells was significantly upregulated.A total of 46 upregulated and 32 downregulated differential expression genes were obtained,which were significantly enriched in signaling pathways such as interleukin-17,tumor necrosis factor-α,nuclear factor kappa B,and Toll-like receptor.TIMP1 and CXCL5 were identified as key core genes related to the development of COPD.[Conclusion]There are significant differences in the distribution of lung tissue cells between COPD and healthy individuals.T cells are closely related to the pathogenesis of COPD and may be potential target cells for prevention and treatment of COPD.The development of COPD involves multiple inflammatory signaling pathways.TIMP1 and CXCL5 are key core genes related to the development of COPD.

chronic obstructive pulmonary diseasesingle-cell transcriptomeT cellsbioinformatics

冯倩、孙岩

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淄博市张店区中医院重症医学科,山东淄博 255000

山东第一医科大学附属省立医院血管外科,山东济南 250021

慢性阻塞性肺疾病 单细胞转录组 T细胞 生物信息学

2024

中国医学工程
中国医药生物技术协会 卫生部肝胆肠外科研究中心

中国医学工程

影响因子:0.504
ISSN:1672-2019
年,卷(期):2024.32(12)