基于单细胞RNA测序分析高内皮细胞小静脉对慢性阻塞性肺疾病患者肺免疫细胞招募作用  

Single-cell RNA sequencing and analysis of high endothelial venule in chronic obstructive pulmonary disease for immune cell recruitment

作　　者：彭玲[1,2] 张华[3] 童霞 张鑫 张兰兰[1] PENG Ling;ZHANG Hua;TONG Xia;ZHANG Xin;ZHANG Lanlan(Department of Respiratory and Critical Care Medicine,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,P.R.China;West China(Airport)Hospital of Sichuan University(The First People’s Hospital of Shuangliu District,Chengdu),Chengdu,Sichuan 610200,P.R.China;West China Second University Hospital,Sichuan University,Chengdu,Sichuan 610041,P.R.China;Division of Gastroenterology,West China Hospital,Sichuan University,Chengdu,Sichuan 610041,P.R.China)

机构地区：[1]四川大学华西医院呼吸与危重症医学科,四川成都610041 [2]四川大学华西空港医院(成都市双流区第一人民医院),四川成都610200 [3]四川大学华西第二医院,四川成都610041 [4]四川大学华西医院消化内科,四川成都610041

出　　处：《中国呼吸与危重监护杂志》2022年第3期170-177,共8页Chinese Journal of Respiratory and Critical Care Medicine

基　　金：国家自然科学基金青年基金(81900065)。

摘　　要：目的在单细胞水平探索高内皮细胞小静脉(high endothelial venule,HEV)在慢性阻塞性肺疾病(简称慢阻肺)中的作用。方法利用GEO公共数据库(GSE136831)中18例慢阻肺患者及28例健康对照组共219257个肺组织单细胞RNA测序结果,分析HEV内皮细胞与T淋巴细胞、B淋巴细胞以及树突状细胞的关系。结果利用生物信息学方法,从这些肺组织单细胞中提取内皮细胞,分选出静脉内皮细胞后,以CCL14、IGFBP7、POSTN作为HEV内皮细胞的标记基因,鉴定出HEV内皮细胞在慢阻肺中的表达上调。通过分析HEV内皮细胞的差异基因的功能,提示存在免疫调节的作用。通过细胞轨迹发育,发现HEV内皮细胞在发育后期富集了细胞外基质的重构。通过受体-配体配对,发现HEV内皮细胞通过一系列配体对T淋巴细胞、B淋巴细胞以及树突状细胞进行招募。结论HEV内皮细胞在慢阻肺中升高,并具有免疫调节的作用。通过分泌一系列的配体后,HEV内皮细胞可招募T淋巴细胞、B淋巴细胞以及树突状细胞进行免疫作用。HEV可能成为慢阻肺治疗的潜在靶标。Objective To explore the role of high endothelial venule(HEV)in chronic obstructive pulmonary disease(COPD)at the single cell level.Methods A total of 219257 cells from the lung tissues of 18 COPD patients and 28 healthy controls in the GEO public database(GSE136831)were used to analyze the relationship between HEV with T lymphocytes,B lymphocytes,and dendritic cells.Results Endothelial cells were extracted using single cell analysis technique,and sorting out venous endothelium,CCL14,IGFBP7,POSTN were used as marker genes for HEV endothelial cells.The ratio of HEV endothelial cells was also identified as up-regulated expression in COPD.The function of the differential genes of HEV endothelial cells was analyzed,suggesting the presence of immune regulation.By trajectory analysis,it was suggested that the differential genes of HEV endothelial cells were enriched for extracellular matrix deposition in late development.Finally,by receptor-ligand pairing,it was suggested that HEV endothelial cells was recruited through a series of ligands with T lymphocytes,B lymphocytes,and dendritic cells.Conclusions HEV endothelial cells are elevated in COPD and have an immunomodulatory role by secreting a series of ligands after recruiting T lymphocytes,B lymphocytes as well as dendritic cells for immune action.HEV may be a potential target for the study of COPD therapy.

关 键 词：计算生物学 生物信息学 高内皮细胞小静脉 慢性阻塞性肺疾病 单细胞测序技术 免疫调节 

分 类 号：R563.9[医药卫生—呼吸系统]