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Transforming primary human hepatocytes into hepatocellular carcinoma with genetically defined factors
Jiang, Zhiwu1; Cheng, Lin2; Wu, Zhiping1; Zhou, Linfu1; Wang, Haitao3; Hong, Qilan2; Wu, Qiting1; Long, Youguo1; Huang, Yunlin1; Xu, Gaoqi2; Yao, Yao1; Tang, Zhaoyang4; Zhang, Zhenfeng5; Yang, Lili6; Luo, Wei7; Yang, Jie8; Gong, Likun9; Liu, Pentao10; Chen, Xinwen1; Cui, Shuzhong11; Zhang, Qi12; Li, Yinxiong1; Li, Peng1,2,13
2022-04
Source PublicationEMBO Reports
ISSN1469-221X
Abstract

Our understanding of human hepatocellular carcinoma (HCC) development and progression has been hampered by the lack of in vivo models. We performed a genetic screen of 10 oncogenes and genetic mutations in Fah-ablated immunodeficient mice in which primary human hepatocytes (PHHs) are used to reconstitute a functional human liver. We identified that MYC, TP53, and KRAS are highly expressed in induced HCC (iHCC) samples. The overexpression of MYC and TP53 transform PHHs into iHCC in situ, though the addition of KRAS significantly increases the tumorigenic efficiency. iHCC, which recapitulate the histological architecture and gene expression characteristics of clinical HCC samples, reconstituted HCC after serial transplantations. Transcriptomic analysis of iHCC and PHHs showed that MUC1 and FAP are expressed in iHCC but not in normal livers. Chimeric antigen receptor (CAR) T cells against these two surface markers efficiently lyse iHCC cells. The properties of iHCC model provide a biological basis for several clinical hallmarks of HCC, and iHCC may serve as a model to study HCC initiation and to identify diagnostic biomarkers and targets for cellular immunotherapy.

KeywordBiomarkers Hepatocellular Carcinoma Humanized Mouse Models Immunotherapy Oncogenes
DOI10.15252/embr.202154275
URLView the original
Indexed BySCIE
Language英語English
WOS Research AreaBiochemistry & Molecular Biology ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Cell Biology
WOS IDWOS:000783458200001
Scopus ID2-s2.0-85128257629
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Cited Times [WOS]:0   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Corresponding AuthorLi, Yinxiong; Li, Peng
Affiliation1.China-New Zealand Joint Laboratory on Biomedicine and Health, State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Center for Cell Regeneration and Biological Therapies, Guangzhou Institut
2.Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, China
3.Cancer Center, Faculty of Health Sciences, University of Macau, Macao
4.Hunan Zhaotai Biomedicine Co. Ltd., Changsha, China
5.The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
6.Department of Nutrition, Guangdong Provincial Key Laboratory of Food, School of Public Health, Sun Yat-sen University, Guangzhou, China
7.Clinical Research Institute, The First People's Hospital of Foshan, Foshan, Guangdong, China
8.Guangdong Women and Children Hospital, Panyu, Guangzhou, China
9.Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhang Jiang Hi-Tech Park, Shanghai, China
10.School of Biomedical Sciences, Stem Cell, and Regenerative Medicine Consortium, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
11.Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou, China
12.Guangdong Key Laboratory of Liver Disease Research, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
13.Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong
Recommended Citation
GB/T 7714
Jiang, Zhiwu,Cheng, Lin,Wu, Zhiping,et al. Transforming primary human hepatocytes into hepatocellular carcinoma with genetically defined factors[J]. EMBO Reports,2022.
APA Jiang, Zhiwu.,Cheng, Lin.,Wu, Zhiping.,Zhou, Linfu.,Wang, Haitao.,Hong, Qilan.,Wu, Qiting.,Long, Youguo.,Huang, Yunlin.,Xu, Gaoqi.,Yao, Yao.,Tang, Zhaoyang.,Zhang, Zhenfeng.,Yang, Lili.,Luo, Wei.,Yang, Jie.,Gong, Likun.,Liu, Pentao.,Chen, Xinwen.,...&Li, Peng.(2022).Transforming primary human hepatocytes into hepatocellular carcinoma with genetically defined factors.EMBO Reports.
MLA Jiang, Zhiwu,et al."Transforming primary human hepatocytes into hepatocellular carcinoma with genetically defined factors".EMBO Reports (2022).
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