Expansion and differentiation of human hepatocyte-derived liver progenitor-like cells and their use for the study of hepatotropic pathogens.
Expansion and differentiation of human hepatocyte-derived liver progenitor-like cells and their use for the study of hepatotropic pathogens.
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人肝细胞来源的肝祖样细胞的扩增和分化及其在嗜肝病原体研究中的应用
DOI：
10.1038/s41422-018-0103-x
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发表时间：
2019-01
期刊：
影响因子：
44.1
通讯作者：
Yan HX
中科院分区：
文献类型：
--
作者：
Fu GB;Huang WJ;Zeng M;Zhou X;Wu HP;Liu CC;Wu H;Weng J;Zhang HD;Cai YC;Ashton C;Ding M;Tang D;Zhang BH;Gao Y;Yu WF;Zhai B;He ZY;Wang HY;Yan HX
人类肝脏疾病的病理生理学机制的研究受到限制，无法在体外扩增原代肝细胞，同时保持增殖能力和代谢功能。我们和其他人以前已经表明，小鼠成熟肝细胞可以在体外转化为肝祖细胞样细胞与定义的化学因子。在这里，我们描述了一个协议，实现有效的转换人原代肝细胞成肝祖细胞样细胞（HepLPC）通过交付发展相关的线索，包括NAD +依赖性脱乙酰酶SIRT1信号。这些HepLPCs可以在体外传代过程中显着扩增。扩增的细胞可以在体外和体内移植后容易地转化回代谢功能性肝细胞。在三维培养条件下，由HepLPC产生的分化细胞恢复了支持B型肝炎病毒（HBV）感染或再活化的能力。我们的工作证明了肝细胞和肝祖细胞样细胞之间的转换用于研究HBV生物学和抗病毒治疗的实用性。这些发现将促进肝脏疾病和再生医学的研究。
The study of pathophysiological mechanisms in human liver disease has been constrained by the inability to expand primary hepatocytes in vitro while maintaining proliferative capacity and metabolic function. We and others have previously shown that mouse mature hepatocytes can be converted to liver progenitor-like cells in vitro with defined chemical factors. Here we describe a protocol achieving efficient conversion of human primary hepatocytes into liver progenitor-like cells (HepLPCs) through delivery of developmentally relevant cues, including NAD + -dependent deacetylase SIRT1 signaling. These HepLPCs could be expanded significantly during in vitro passage. The expanded cells can readily be converted back into metabolically functional hepatocytes in vitro and upon transplantation in vivo. Under three-dimensional culture conditions, differentiated cells generated from HepLPCs regained the ability to support infection or reactivation of hepatitis B virus (HBV). Our work demonstrates the utility of the conversion between hepatocyte and liver progenitor-like cells for studying HBV biology and antiviral therapies. These findings will facilitate the study of liver diseases and regenerative medicine.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
DOI：
10.1007/978-1-4939-6700-1_6
发表时间：
2017-01-01
期刊：
HEPATITIS B VIRUS: METHODS AND PROTOCOLS
影响因子：
--
作者：
Xia, Yuchen;Stadler, Daniela;Protzer, Ulrike
通讯作者：
Protzer, Ulrike
影响因子：
64.5
作者：
Huch M;Gehart H;van Boxtel R;Hamer K;Blokzijl F;Verstegen MM;Ellis E;van Wenum M;Fuchs SA;de Ligt J;van de Wetering M;Sasaki N;Boers SJ;Kemperman H;de Jonge J;Ijzermans JN;Nieuwenhuis EE;Hoekstra R;Strom S;Vries RR;van der Laan LJ;Cuppen E;Clevers H
通讯作者：
Clevers H
影响因子：
19
作者：
Federation, Alexander J.;Bradner, James E.;Meissner, Alexander
通讯作者：
Meissner, Alexander
影响因子：
23.9
作者：
Han, Myung-Kwan;Song, Eun-Kyung;Broxmeyer, Hal E.
通讯作者：
Broxmeyer, Hal E.