Single-cell RNA sequencing reveals heterogeneous tumor and immune cell populations in early-stage lung adenocarcinomas harboring EGFR mutations

doi:10.1038/s41388-020-01528-0

	Single-cell RNA sequencing reveals heterogeneous tumor and immune cell populations in early-stage lung adenocarcinomas harboring EGFR mutations
	He, Di 1,2; Wang, Di 2; Lu, Ping 3; Yang, Nan 4; Xue, Zhigang 3; Zhu, Xianmin1,2 ; Zhang, Peng 2; Fan, Guoping1,5
	2021-01-14
发表期刊	ONCOGENE
ISSN	0950-9232
发表状态	已发表
DOI	10.1038/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.
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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).