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

doi:10.1038/s41556-019-0359-5

	Modelling liver cancer initiation with organoids derived from directly reprogrammed human hepatocytes
	Sun, Lulu 1; Wang, Yuqing 2; Cen, Jin 1; Ma, Xiaolong 1; Cui, Lei 1; Qiu, Zhixin 1; Zhang, Zhengtao 1; Li, Hong 3; Yang, Run-Zhou 4; Wang, Chenhua 1; Chen, Xiaotao 1; Wang, Le 5; Ye, Yao 6; Zhang, Haibin 7; Pan, Guoyu 5; Kang, Jian-Sheng 8; Ji, Yuan 6; Zheng, Yun-Wen 9,10,11; Zheng, Shan 2; Hui, Lijian1,12,13,14
	2019-08
发表期刊	NATURE CELL BIOLOGY (IF:17.3[JCR-2023],24.2[5-Year])
ISSN	1465-7392
卷号	21 期号:8 页码:1015-+
发表状态	已发表
DOI	10.1038/s41556-019-0359-5
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.
收录类别	SCI ; SCIE
语种	英语
资助项目	National Science and Technology Major Project[2018ZX09711002-009]
WOS研究方向	Cell Biology
WOS类目	Cell Biology
WOS记录号	WOS:000478029000013
出版者	NATURE PUBLISHING GROUP
WOS关键词	INTRAHEPATIC CHOLANGIOCARCINOMA ; HEPATOCELLULAR-CARCINOMA ; COLORECTAL-CANCER ; GENE-EXPRESSION ; ADULT LIVER ; CELL ; MITOCHONDRIA ; REVEALS ; MYC ; ENRICHMENT
原始文献类型	Article
引用统计	正在获取...
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/61130
专题	生命科学与技术学院_特聘教授组_惠利健组
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 11.Jiangsu Univ, Inst Regenerat Med, Zhenjiang, Jiangsu, Peoples R China 12.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 13.Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing, Peoples R China 14.Chinese Acad Sci, Biores Innovat Ctr, Shanghai Inst Biochem & Cell Biol, Suzhou, Peoples R China
通讯作者单位	生命科学与技术学院
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-+.