Modelling liver cancer initiation with organoids derived from directly reprogrammed human hepatocytes
文献类型：期刊论文
| 作者 | Sun, Lulu5; Cen, Jin5; Ma, Xiaolong5; Cui, Lei5; Qiu, Zhixin5; Zhang, Zhengtao5; Wang, Chenhua5; Chen, Xiaotao5; Hui, Lijian5; Wang, Yuqing6 |
| 刊名 | NATURE CELL BIOLOGY
 |
| 出版日期 | 2019 |
| 卷号 | 21期号:8页码:1015-+ |
| ISSN号 | 1465-7392 |
| DOI | 10.1038/s41556-019-0359-5 |
| 文献子类 | Article |
| 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. |
| 学科主题 | Cell Biology |
| WOS关键词 | INTRAHEPATIC CHOLANGIOCARCINOMA ; HEPATOCELLULAR-CARCINOMA ; COLORECTAL-CANCER ; GENE-EXPRESSION ; ADULT LIVER ; CELL ; MITOCHONDRIA ; REVEALS ; MYC ; ENRICHMENT |
| 语种 | 英语 |
| WOS记录号 | WOS:000478029000013 |
| 出版者 | NATURE PUBLISHING GROUP |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/997]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Yokohama City Univ, Sch Med, Yokohama, Kanagawa, Japan; 2.Univ Tsukuba, Fac Med, Tsukuba, Ibaraki, Japan; 3.Zhengzhou Univ, Affiliated Hosp 1, Zhengzhou, Henan, Peoples R China; 4.Chinese Acad Sci, Biores Innovat Ctr, Shanghai Inst Biochem & Cell Biol, Suzhou, Peoples R China, 5.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; 6.Fudan Univ, Dept Pediat Surg, Childrens Hosp, Shanghai, Peoples R China; 7.Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing, Peoples R China; 8.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China; 9.Jiangsu Univ, Inst Regenerat Med, Zhenjiang, Jiangsu, Peoples R China; 10.Second Mil Med Univ, Eastern Hepatobiliary Surg Hosp, Dept Hepat Surg 5, Shanghai, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Sun, Lulu,Cen, Jin,Ma, Xiaolong,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.,Cen, Jin.,Ma, Xiaolong.,Cui, Lei.,Qiu, Zhixin.,...&,.(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：上海营养与健康研究所
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