首页|单细胞RNA测序联合实验验证树突状细胞在慢性阻塞性肺疾病中的核心基因

单细胞RNA测序联合实验验证树突状细胞在慢性阻塞性肺疾病中的核心基因

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目的 单细胞RNA测序(scRNA-Seq)联合实验验证树突状细胞在慢性阻塞性肺疾病(COPD)中的核心基因.方法 从基因表达数据集(GEO)数据库下载单细胞数据GSE173896和芯片数据GSE38974.GSE173896进行质控、批次矫正、降维聚类、细胞类型注释及组间树突状细胞差异表达基因(DC-DEG)鉴定.GSE38974差异分析得到的差异基因(DEG)与DC-DEG取交集获取共有DC-DEG,评估共有DC-DEG对COPD的诊断效能和共有DC-DEG富集分析及其与GSE38974免疫细胞浸润中激活的树突状细胞(DC)、浆细胞样树突状细胞(pDC)和Th17细胞的相关性.肺气肿小鼠模型肺组织对共有DC-DEG的mRNA表达量进行实验验证.结果 GSE173896得到组间DC-DEG 18个,GSE38974得到646个DEG,两者取交集得到3个DC-DEG,包括白细胞介素1受体拮抗剂(IL1RN)、S100钙结合蛋白A8(S100A8)和S100A9,曲线下面积(AUC)值分别为0.841、0.804和0.966.基因本体论分析(GO)和京都基因与基因组百科全书(KEGG)主要富集于慢性炎症反应、含胶原蛋白的细胞外基质、晚期糖基化终产物受体(RAGE)结合、Toll样受体(TLR)结合、白细胞介素17(IL-17)信号通路等.IL1RN、S100A8和S100A9均与激活的DC、pDC及Th17细胞呈正相关.实验验证结果显示肺气肿小鼠肺组织IL1RN、S100A8和S100A9的mRNA相对表达量上调.结论 IL1RN、S100A8和S100A9可能是DC在COPD发病机制中的核心基因,为后续COPD的免疫治疗提供潜在靶点和理论依据.
Single-cell RNA sequencing combined experimental verifies the core genes of dendritic cells in chronic obstructive pulmonary disease
Objective Single-cell RNA sequencing(scRNA-Seq)and experimental verifies core genes of dendritic cells in chronic obstructive pulmonary disease(COPD).Methods scRNA-seq data GSE173896 and chip data GSE38974 were extracted from the Gene Expression Omnibus(GEO)database.GSE173896 was used to perform quality control,batch correction,dimensionality reduction clustering,cell type annotation and dendritic cell differentially expressed genes(DC-DEGs)identification.DEGs from the analysis of GSE38974 were intersected with DC-DEGs to obtain the common DC-DEGs.The diagnostic efficacy of the common DC-DEGs for COPD and their enrichment analysis were conducted.The correlation of the common DC-DEGs with activated dendritic cell(DCs),plasmacytoid dendritic cell(pDCs)and type 17 T helper(Th17)cells were analyzed.The mRNA expression level of the common DC-DEGs in the lung tissue of emphysema mice was verified.Results From GSE173896,18 DC-DEGs were obtained between groups and from GSE38974,646 DEGs were obtained.The intersection of the two resulted in 3 common DC-DEGs,including interleukin 1 receptor antagonist 1(IL1RN),S100 calcicum-binding protein A8(S100A8)and S100A9.Their respective area under curve(AUC)values were 0.841,0.804 and 0.966.The GO and KEGG enrichment analysis mainly concentrated on chronic inflammatory response,collagen-containing extracellular matrix,receptor for advanced glycation end products(RAGE)binding,Toll-like receptor(TLR)binding and interleukin 17(IL-17)signaling pathway.IL1RN,S100A8 and S100A9 were positively correlated with activated DCs,pDCs and Th17 cells.The results showed that the mRNA relative expression levels of IL1RN,S100A8 and S100A9 were up-regulated in the lung tissue of emphysema mice.Conclusion IL1RN,S100A8 and S100A9 may be the core genes of DCs in the pathogenesis of COPD,which potentially provide targets and a theoretical basis for subsequent COPD immunotherapy.

chronic obstructive pulmonary disease(COPD)single cell RNA sequencing(scRNA-Seq)dendritic cells(DCs)core genes

薛廷、郑乐婷、董菲、周广、钟小宁

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广西医科大学第一附属医院呼吸与危重症医学科,广西南宁 530021

广西医科大学第一附属医院风湿免疫科,广西南宁 530021

慢性阻塞性肺疾病(COPD) 单细胞RNA测序(scRNA-Seq) 树突状细胞(DC) 核心基因

国家自然科学基金国家自然科学基金

8207004482360012

2024

细胞与分子免疫学杂志
中国免疫学会,第四军医大学

细胞与分子免疫学杂志

CSTPCD北大核心
影响因子:0.817
ISSN:1007-8738
年,卷(期):2024.40(2)
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