Single-cell RNA sequencing reveals heterogeneous tumor and immune cell populations in early-stage lung adenocarcinomas harboring EGFR mutations
He, Di1,2; Wang, Di2; Lu, Ping3; Yang, Nan4; Xue, Zhigang3; Zhu, Xianmin1,2; Zhang, Peng2; Fan, Guoping1,5
2021-01-14
发表期刊ONCOGENE
ISSN0950-9232
发表状态已发表
DOI10.1038/s41388-020-01528-0
摘要Lung adenocarcinoma (LUAD) harboring EGFR mutations prevails in Asian population. However, the inter-patient and intra-tumor heterogeneity has not been addressed at single-cell resolution. Here we performed single-cell RNA sequencing (scRNA-seq) of total 125,674 cells from seven stage-I/II LUAD samples harboring EGFR mutations and five tumor-adjacent lung tissues. We identified diverse cell types within the tumor microenvironment (TME) in which myeloid cells and T cells were the most abundant stromal cell types in tumors and adjacent lung tissues. Within tumors, accompanied by an increase in CD1C(+) dendritic cells, the tumor-associated macrophages (TAMs) showed pro-tumoral functions without signature gene expression of defined M1 or M2 polarization. Tumor-infiltrating T cells mainly displayed exhausted and regulatory T-cell features. The adenocarcinoma cells can be categorized into different subtypes based on their gene expression signatures in distinct pathways such as hypoxia, glycolysis, cell metabolism, translation initiation, cell cycle, and antigen presentation. By performing pseudotime trajectory, we found that ELF3 was among the most upregulated genes in more advanced tumor cells. In response to secretion of inflammatory cytokines (e.g., IL1B) from immune infiltrates, ELF3 in tumor cells was upregulated to trigger the activation of PI3K/Akt/NF-kappa B pathway and elevated expression of proliferation and anti-apoptosis genes such as BCL2L1 and CCND1. Taken together, our study revealed substantial heterogeneity within early-stage LUAD harboring EGFR mutations, implicating complex interactions among tumor cells, stromal cells and immune infiltrates in the TME.
URL查看原文
收录类别SCI ; SCIE
语种英语
资助项目National Program on Key Basic Research Project (973 Program)[2015CB964702][2015CB964601] ; National Natural Science Foundation of China[81570521][81470244][81622001][81430026][91642108][31871288] ; Experimental Animal Research Fund, Science and Technology Commission of Shanghai Municipality[18140903900][15140903900]
WOS研究方向Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
WOS类目Biochemistry & Molecular Biology ; Oncology ; Cell Biology ; Genetics & Heredity
WOS记录号WOS:000585016500001
出版者SPRINGERNATURE
引用统计
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/123956
专题免疫化学研究所_特聘教授组_范国平组
免疫化学研究所
通讯作者Zhu, Xianmin; Zhang, Peng; Fan, Guoping
作者单位1.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China
2.Tongji Univ, Shanghai Pulm Hosp, Sch Life Sci & Technol, Dept Thorac Surg, Shanghai 200433, Peoples R China
3.Tongji Univ, Tongji Hosp, Translat Ctr Stem Cell Res, Dept Regenerat Med,Sch Med, Shanghai 200065, Peoples R China
4.Zhangjiang High Tech Pk Ltd, PharmaLegacy Labs Shanghai Co, Bldg 7,388 Jialilue Rd, Shanghai 201203, Peoples R China
5.Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA
第一作者单位免疫化学研究所
通讯作者单位免疫化学研究所
第一作者的第一单位免疫化学研究所
推荐引用方式
GB/T 7714
He, Di,Wang, Di,Lu, Ping,et al. Single-cell RNA sequencing reveals heterogeneous tumor and immune cell populations in early-stage lung adenocarcinomas harboring EGFR mutations[J]. ONCOGENE,2021.
APA He, Di.,Wang, Di.,Lu, Ping.,Yang, Nan.,Xue, Zhigang.,...&Fan, Guoping.(2021).Single-cell RNA sequencing reveals heterogeneous tumor and immune cell populations in early-stage lung adenocarcinomas harboring EGFR mutations.ONCOGENE.
MLA He, Di,et al."Single-cell RNA sequencing reveals heterogeneous tumor and immune cell populations in early-stage lung adenocarcinomas harboring EGFR mutations".ONCOGENE (2021).
条目包含的文件 下载所有文件
文件名称/大小 文献类型 版本类型 开放类型 使用许可
个性服务
查看访问统计
谷歌学术
谷歌学术中相似的文章
[He, Di]的文章
[Wang, Di]的文章
[Lu, Ping]的文章
百度学术
百度学术中相似的文章
[He, Di]的文章
[Wang, Di]的文章
[Lu, Ping]的文章
必应学术
必应学术中相似的文章
[He, Di]的文章
[Wang, Di]的文章
[Lu, Ping]的文章
相关权益政策
暂无数据
收藏/分享
文件名: 10.1038@s41388-020-01528-0.pdf
格式: Adobe PDF
此文件暂不支持浏览
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。