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Large-scale Generation of Functional and Transplantable Hepatocytes and Cholangiocytes from Human Endoderm Stem Cells
Feng, Sisi1; Wu, Jiaying1; Qiu, Wei-Lin2,3; Yang, Li2,4; Deng, Xiaogang1; Zhou, Ying1; Chen, Yabin5; Li, Xiao1; Yu, Lei6; Li, Hongsheng1
刊名CELL REPORTS
2020-12-08
卷号33期号:10页码:24
ISSN号2211-1247
DOI10.1016/j.celrep.2020.108455
通讯作者Yin, Hao(roytina0241032@hotmail.com) ; Chen, Luonan(lnchen@sibs.ac.cn) ; Xu, Cheng-Ran(cxu@pku.edu.cn) ; Cheng, Xin(xcheng@sibcb.ac.cn)
英文摘要The ever-increasing therapeutic and pharmaceutical demand for liver cells calls for systems that enable mass production of hepatic cells. Here we describe a large-scale suspension system that uses human endoderm stem cells (hEnSCs) as precursors to generate functional and transplantable hepatocytes (E-heps) or cholangiocytes (E-chos). hEnSC-derived hepatic populations are characterized by single-cell transcriptomic analyses and compared with hESC-derived counterparts, in-vitro-maintained or -expanded primary hepatocytes and adult cells, which reveals that hepatic differentiation of hEnSCs recapitulates in vivo development and that the heterogeneities of the resultant populations can be manipulated by regulating the EGF and MAPK signaling pathways. Functional assessments demonstrate that E-heps and E-chos possess properties comparable with adult counterparts and that, when transplanted intraperitoneally, encapsulated E-heps were able to rescue rats with acute liver failure. Our study lays the foundation for cell-based therapeutic agents and in vitro applications for liver diseases.
资助项目National Key R&D Program of China[2017YFA0102702] ; National Key R&D Program of China[2017YFA0504501] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA16020203] ; National Natural Science Foundation of China[31771061] ; Scientific Instrument Developing Project of the Chinese Academy of Sciences[YJKYYQ20170042] ; Science and Technology Commission of Shanghai Municipality[15JC1400201] ; National Key Research and Development Program of China[2019YFA0801500] ; National Basic Research Program of China (973 Program)[2015CB942800]
WOS关键词RNA-SEQ ; IN-VITRO ; DIFFERENTIATION ; FIBROBLASTS ; MECHANISMS
WOS研究方向Cell Biology
语种英语
出版者CELL PRESS
WOS记录号WOS:000596872600009
内容类型期刊论文
源URL[http://119.78.100.183/handle/2S10ELR8/296356]  
专题中国科学院上海药物研究所
通讯作者Yin, Hao; Chen, Luonan; Xu, Cheng-Ran; Cheng, Xin
作者单位1.Chinese Acad Sci, Univ Chinese Acad Sci, State Key Lab Cell Biol, CAS Ctr Excellence Mol Cell Sci,Inst Biochem & Ce, Shanghai 200031, Peoples R China
2.Peking Univ, Coll Life Sci, Peking Tsinghua Ctr Life Sci, Minist Educ,Key Lab Cell Proliferat & Differentia, Beijing 10087, Peoples R China
3.Peking Univ, PKU Tsinghua NIBS Grad Program, Beijing 100871, Peoples R China
4.Peking Univ, Acad Adv Interdisciplinary Studies, Beijing 100871, Peoples R China
5.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 200031, Peoples R China
6.Fudan Univ, Zhongshan Hosp, Liver Canc Inst,Minist Educ, Key Lab Carcinogenesis & Canc Invas,Dept Liver Su, Shanghai 200032, Peoples R China
7.Nanjing Univ, Dept Hepatobiliary Surg, Affiliated Drum Tower Hosp, Med Sch, Nanjing 21008, Peoples R China
8.Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA
9.Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA
10.Chinese Acad Sci, Ctr Drug Safety Evaluat & Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714
Feng, Sisi,Wu, Jiaying,Qiu, Wei-Lin,et al. Large-scale Generation of Functional and Transplantable Hepatocytes and Cholangiocytes from Human Endoderm Stem Cells[J]. CELL REPORTS,2020,33(10):24.
APA Feng, Sisi.,Wu, Jiaying.,Qiu, Wei-Lin.,Yang, Li.,Deng, Xiaogang.,...&Cheng, Xin.(2020).Large-scale Generation of Functional and Transplantable Hepatocytes and Cholangiocytes from Human Endoderm Stem Cells.CELL REPORTS,33(10),24.
MLA Feng, Sisi,et al."Large-scale Generation of Functional and Transplantable Hepatocytes and Cholangiocytes from Human Endoderm Stem Cells".CELL REPORTS 33.10(2020):24.
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