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Modelling liver cancer initiation with organoids derived from directly reprogrammed human hepatocytes

文献类型：期刊论文

作者Sun, Lulu1; Wang, Yuqing2; Cen, Jin1; Ma, Xiaolong1; Cui, Lei1; Qiu, Zhixin1; Zhang, Zhengtao1; Li, Hong3; Yang, Run-Zhou4; Wang, Chenhua1
刊名NATURE CELL BIOLOGY
出版日期2019-08-01
卷号21期号:8页码:1015-+
ISSN号1465-7392
DOI10.1038/s41556-019-0359-5
通讯作者Zheng, Yun-Wen(ywzheng@md.tsukuba.ac.jp) ; Zheng, Shan(szheng@shmu.edu.cn) ; Hui, Lijian(ljhui@sibcb.ac.cn)
英文摘要Human liver cancers, including hepatocellular carcinomas and intra-hepatic cholangiocarcinomas, are often diagnosed late with poor prognosis. A better understanding of cancer initiation could provide potential preventive therapies and increase survival. Models for studying human liver cancer initiation are largely missing. Here, using directly reprogrammed human hepatocytes (hiHeps) and inactivation of p53 and RB, we established organoids possessing liver architecture and function. HiHep organoids were genetically engineered to model the initial alterations in human liver cancers. Bona fide hepatocellular carcinomas were developed by overexpressing c-Myc. Excessive mitochondrion-endoplasmic reticulum coupling induced by c-Myc facilitated hepatocellular carcinoma initiation and seemed to be a target of preventive treatment. Furthermore, through the analysis of human intra-hepatic cholangiocarcinoma-enriched mutations, we demonstrate that the RAS-induced lineage conversion from hepatocytes to intra-hepatic cholangiocarcinoma cells can be prevented by the combined inhibition of Notch and JAK-STAT. Together, hiHep organoids represent a system that can be genetically manipulated to model cancer initiation and identify potential preventive therapies.
WOS关键词INTRAHEPATIC CHOLANGIOCARCINOMA ; HEPATOCELLULAR-CARCINOMA ; COLORECTAL-CANCER ; GENE-EXPRESSION ; ADULT LIVER ; CELL ; MITOCHONDRIA ; REVEALS ; MYC ; ENRICHMENT
资助项目Chinese Academy of Sciences[XDA16020201] ; Chinese Academy of Sciences[XDA12050104] ; Chinese Academy of Sciences[153D31KYSB20160247] ; National Natural Science Foundation of China[31630044] ; National Natural Science Foundation of China[31601186] ; National Natural Science Foundation of China[81703093] ; National Natural Science Foundation of China[31801228] ; Shanghai Science and Technology Committee[16JC1400202] ; National Science and Technology Major Project[2018ZX09711002-009] ; National Special Support Plan for Top Talents
WOS研究方向Cell Biology
语种英语
WOS记录号WOS:000478029000013
出版者NATURE PUBLISHING GROUP
源URL[http://119.78.100.183/handle/2S10ELR8/289130]  
专题中国科学院上海药物研究所
通讯作者Zheng, Yun-Wen; Zheng, Shan; Hui, Lijian
作者单位1.Univ Chinese Acad Sci, Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai Inst Biochem & Cell Biol,State Key Lab C, Shanghai, Peoples R China
2.Fudan Univ, Dept Pediat Surg, Childrens Hosp, Shanghai, Peoples R China
3.Chinese Acad Sci, CAS MPG Partner Inst Computat Biol, Shanghai Inst Biol Sci, Key Lab Computat Biol, Shanghai, Peoples R China
4.Univ Chinese Acad Sci, Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Shanghai, Peoples R China
5.Chinese Acad Sci, Ctr Drug Safety Evaluat & Res, Shanghai Inst Mat Med, Shanghai, Peoples R China
6.Fudan Univ, Zhongshan Hosp, Dept Pathol, Shanghai, Peoples R China
7.Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Hepat Surg 5, Shanghai, Peoples R China
8.Zhengzhou Univ, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China
9.Univ Tsukuba, Fac Med, Tsukuba, Ibaraki, Japan
10.Yokohama City Univ, Sch Med, Yokohama, Kanagawa, Japan
推荐引用方式
GB/T 7714		 Sun, Lulu,Wang, Yuqing,Cen, Jin,et al. Modelling liver cancer initiation with organoids derived from directly reprogrammed human hepatocytes[J]. NATURE CELL BIOLOGY,2019,21(8):1015-+.
APA Sun, Lulu.,Wang, Yuqing.,Cen, Jin.,Ma, Xiaolong.,Cui, Lei.,...&Hui, Lijian.(2019).Modelling liver cancer initiation with organoids derived from directly reprogrammed human hepatocytes.NATURE CELL BIOLOGY,21(8),1015-+.
MLA Sun, Lulu,et al."Modelling liver cancer initiation with organoids derived from directly reprogrammed human hepatocytes".NATURE CELL BIOLOGY 21.8(2019):1015-+.

入库方式： OAI收割

来源：上海药物研究所

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