Single cell-spatial transcriptomics and bulk multi-omics analysis of heterogeneity and ecosystems in hepatocellular carcinoma

被引：7

作者：

Ye, Jiazhou ^{[1
]}

Lin, Yan ^{[2
]}

Liao, Zhiling ^{[3
]}

Gao, Xing ^{[2
]}

Lu, Cheng ^{[1
]}

Lu, Lu ^{[2
]}

Huang, Julu ^{[1
]}

Huang, Xi ^{[2
]}

Huang, Shilin ^{[2
]}

Yu, Hongping ^{[4
]}

Bai, Tao ^{[1
]}

Chen, Jie ^{[1
]}

Wang, Xiaobo ^{[1
]}

Xie, Mingzhi ^{[2
]}

Luo, Min ^{[2
]}

Zhang, Jinyan ^{[2
]}

Wu, Feixiang ^{[1
]}

Wu, Guobin ^{[1
]}

Ma, Liang ^{[1
]}

Xiang, Bangde ^{[1
]}

Li, Lequn ^{[1
]}

Li, Yongqiang ^{[2
]}

Luo, Xiaoling ^{[4
]}

Liang, Rong ^{[2
]}

机构：

[1] Guangxi Med Univ, Canc Hosp, Dept Hepatobiliary Surg, Nanning, Peoples R China

[2] Guangxi Med Univ, Canc Hosp, Dept Digest Oncol, Nanning, Peoples R China

[3] Guangxi Med Univ, Canc Hosp, Dept Pathol, Nanning, Peoples R China

[4] Guangxi Med Univ, Canc Hosp, Dept Expt Res, Nanning, Peoples R China

来源：

NPJ PRECISION ONCOLOGY | 2024年 / 8卷 / 01期

基金：

中国国家自然科学基金;

关键词：

T-CELLS; TUMOR EVOLUTION; METABOLISM; GROWTH; SUPPRESSION; INHIBITION; LANDSCAPE; PHENOTYPE; STEMNESS; DYNAMICS;

D O I：

10.1038/s41698-024-00752-1

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

This study profiled global single cell-spatial-bulk transcriptome landscapes of hepatocellular carcinoma (HCC) ecosystem from six HCC cases and a non-carcinoma liver control donor. We discovered that intratumoral heterogeneity mainly derived from HCC cells diversity and pervaded the genome-transcriptome-proteome-metabolome network. HCC cells are the core driving force of taming tumor-associated macrophages (TAMs) with pro-tumorigenic phenotypes for favor its dominant growth. Remarkably, M1-types TAMs had been characterized by disturbance of metabolism, poor antigen-presentation and immune-killing abilities. Besides, we found simultaneous cirrhotic and HCC lesions in an individual patient shared common origin and displayed parallel clone evolution via driving disparate immune reprograms for better environmental adaptation. Moreover, endothelial cells exhibited phenotypically conserved but executed differential functions in a space-dependent manner. Further, the spatiotemporal traits of rapid recurrence niche genes were identified and validated by immunohistochemistry. Our data unravels the great significance of HCC cells in shaping vibrant tumor ecosystems corresponding to clinical scenarios.

引用

页数：18

共 112 条

[91] Metabolic reprogramming of macrophages during infections and cancer [J].

Wang, Shiyao ;

Liu, Ruichen ;

Yu, Qing ;

Dong, Lin ;

Bi, Yujing ;

Liu, Guangwei .

CANCER LETTERS, 2019, 452 :14-22

[92]

Wang Y., 2019, bioRxiv, DOI DOI 10.1101/507871

[93] Spatial maps of hepatocellular carcinoma transcriptomes reveal spatial expression patterns in tumor immune microenvironment [J].

Wang, Yue-fan ;

Yuan, Sheng-xian ;

Jiang, Hui ;

Li, Zhi-xuan ;

Yin, Hao-zan ;

Tan, Jian ;

Dai, Zhi-hui ;

Ge, Chun-mei ;

Sun, Shu-han ;

Yang, Fu .

THERANOSTICS, 2022, 12 (09) :4163-4180

[94] Engineered SIRPα Variants as Immunotherapeutic Adjuvants to Anticancer Antibodies [J].

Weiskopf, Kipp ;

Ring, Aaron M. ;

Ho, Chia Chi M. ;

Volkmer, Jens-Peter ;

Levin, Aron M. ;

Volkmer, Anne Kathrin ;

Oezkan, Engin ;

Fernhoff, Nathaniel B. ;

van de Rijn, Matt ;

Weissman, Irving L. ;

Garcia, K. Christopher .

SCIENCE, 2013, 341 (6141) :88-91

[95] Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities [J].

Wen, Yankai ;

Lambrecht, Joeri ;

Ju, Cynthia ;

Tacke, Frank .

CELLULAR & MOLECULAR IMMUNOLOGY, 2021, 18 (01) :45-56

[96] Epithelial keratins: Biology and implications as diagnostic markers for liquid biopsies [J].

Werner, Stefan ;

Keller, Laura ;

Pantel, Klaus .

MOLECULAR ASPECTS OF MEDICINE, 2020, 72

[97] Mitochondrial metabolism coordinates stage-specific repair processes in macrophages during wound healing [J].

Willenborg, Sebastian ;

Sanin, David E. ;

Jais, Alexander ;

Ding, Xiaolei ;

Ulas, Thomas ;

Nuechel, Julian ;

Popovic, Milica ;

MacVicar, Thomas ;

Langer, Thomas ;

Schultze, Joachim L. ;

Gerbaulet, Alexander ;

Roers, Axel ;

Pearce, Edward J. ;

Bruening, Jens C. ;

Trifunovic, Aleksandra ;

Eming, Sabine A. .

CELL METABOLISM, 2021, 33 (12) :2398-+

[98] Comprehensive analysis of spatial architecture in primary liver cancer [J].

Wu, Rui ;

Guo, Wenbo ;

Qiu, Xinyao ;

Wang, Shicheng ;

Sui, Chengjun ;

Lian, Qiuyu ;

Wu, Jianmin ;

Shan, Yiran ;

Yang, Zhao ;

Yang, Shuai ;

Wu, Tong ;

Wang, Kaiting ;

Zhu, Yanjing ;

Wang, Shan ;

Liu, Changyi ;

Zhang, Yangqianwen ;

Zheng, Bo ;

Li, Zhixuan ;

Zhang, Yani ;

Shen, Siyun ;

Zhao, Yan ;

Wang, Wenwen ;

Bao, Jinxia ;

Hu, Ji ;

Wu, Xuan ;

Jiang, Xiaoqing ;

Wang, Hongyang ;

Gu, Jin ;

Chen, Lei .

SCIENCE ADVANCES, 2021, 7 (51)

[99] Lipid Metabolism in Regulation of Macrophage Functions [J].

Yan, Jiawei ;

Horng, Tiffany .

TRENDS IN CELL BIOLOGY, 2020, 30 (12) :979-989

[100] A global view of hepatocellular carcinoma: trends, risk, prevention and management [J].

Yang, Ju Dong ;

Hainaut, Pierre ;

Gores, Gregory J. ;

Amadou, Amina ;

Plymoth, Amelie ;

Roberts, Lewis R. .

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY, 2019, 16 (10) :589-604

← 3 4 5 6 7 8 9 10 11 12 →