Long-term functional maintenance of primary human hepatocytes in vitro

Chengang Xiang; Yuanyuan Du; Gaofan Meng; Liew Soon Yi; Shicheng Sun; Nan Song; Xiaonan Zhang; Yiwei Xiao; Jie Wang; Zhigang Yi; Yifang Liu; Bingqing Xie; Min Wu; Jun Shu; Da Sun; Jun Jia; Zhen Liang; Dong Sun; Yanxiang Huang; Yan Shi; Jun Xu; Fengmin Lu; Cheng Li; Kuanhui Xiang; Zhenghong Yuan; Shichun Lu; Hongkui Deng

doi:10.1126/science.aau7307

Long-term functional maintenance of primary human hepatocytes in vitro

Chengang Xiang, Yuanyuan Du, Gaofan Meng, Liew Soon Yi, Shicheng Sun, Nan Song, Xiaonan Zhang, Yiwei Xiao, Jie Wang, Zhigang Yi, Yifang Liu, Bingqing Xie, Min Wu, Jun Shu, Da Sun, Jun Jia, Zhen Liang, Dong Sun, Yanxiang Huang, Yan ShiJun Xu, Fengmin Lu, Cheng Li, Kuanhui Xiang, Zhenghong Yuan, Shichun Lu, Hongkui Deng

Research output: Contribution to journal › Review article › peer-review

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Abstract

The maintenance of terminally differentiated cells, especially hepatocytes, in vitro has proven challenging. Here we demonstrated the long-term in vitro maintenance of primary human hepatocytes (PHHs) by modulating cell signaling pathways with a combination of five chemicals (5C). 5C-cultured PHHs showed global gene expression profiles and hepatocyte-specific functions resembling those of freshly isolated counterparts. Furthermore, these cells efficiently recapitulated the entire course of hepatitis B virus (HBV) infection over 4 weeks with the production of infectious viral particles and formation of HBV covalently closed circular DNA. Our study demonstrates that, with a chemical approach, functional maintenance of PHHs supports long-term HBV infection in vitro, providing an efficient platform for investigating HBV cell biology and antiviral drug screening.

Original language	English
Pages (from-to)	399-402
Number of pages	4
Journal	Science
Volume	364
Issue number	6438
DOIs	https://doi.org/10.1126/science.aau7307
Publication status	Published - 26 Apr 2019
Externally published	Yes

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@article{211fb70488cc4425b20e649846193356,

title = "Long-term functional maintenance of primary human hepatocytes in vitro",

abstract = "The maintenance of terminally differentiated cells, especially hepatocytes, in vitro has proven challenging. Here we demonstrated the long-term in vitro maintenance of primary human hepatocytes (PHHs) by modulating cell signaling pathways with a combination of five chemicals (5C). 5C-cultured PHHs showed global gene expression profiles and hepatocyte-specific functions resembling those of freshly isolated counterparts. Furthermore, these cells efficiently recapitulated the entire course of hepatitis B virus (HBV) infection over 4 weeks with the production of infectious viral particles and formation of HBV covalently closed circular DNA. Our study demonstrates that, with a chemical approach, functional maintenance of PHHs supports long-term HBV infection in vitro, providing an efficient platform for investigating HBV cell biology and antiviral drug screening.",

keywords = "Antiviral Agents/isolation & purification, DNA, Circular/biosynthesis, DNA, Viral/biosynthesis, Drug Evaluation, Preclinical, Hepatitis B virus/drug effects, Hepatocytes/drug effects, Humans, Primary Cell Culture/methods, Transcriptome, Virion/drug effects, Virus Cultivation/methods",

author = "Chengang Xiang and Yuanyuan Du and Gaofan Meng and {Soon Yi}, Liew and Shicheng Sun and Nan Song and Xiaonan Zhang and Yiwei Xiao and Jie Wang and Zhigang Yi and Yifang Liu and Bingqing Xie and Min Wu and Jun Shu and Da Sun and Jun Jia and Zhen Liang and Dong Sun and Yanxiang Huang and Yan Shi and Jun Xu and Fengmin Lu and Cheng Li and Kuanhui Xiang and Zhenghong Yuan and Shichun Lu and Hongkui Deng",

note = "Copyright {\textcopyright} 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.",

year = "2019",

month = apr,

day = "26",

doi = "10.1126/science.aau7307",

language = "English",

volume = "364",

pages = "399--402",

journal = "Science",

issn = "1095-9203",

publisher = "American Association for the Advancement of Science (AAAS)",

number = "6438",

}

Xiang, C, Du, Y, Meng, G, Soon Yi, L, Sun, S, Song, N, Zhang, X, Xiao, Y, Wang, J, Yi, Z, Liu, Y, Xie, B, Wu, M, Shu, J, Sun, D, Jia, J, Liang, Z, Sun, D, Huang, Y, Shi, Y, Xu, J, Lu, F, Li, C, Xiang, K, Yuan, Z, Lu, S & Deng, H 2019, 'Long-term functional maintenance of primary human hepatocytes in vitro', Science, vol. 364, no. 6438, pp. 399-402. https://doi.org/10.1126/science.aau7307

TY - JOUR

T1 - Long-term functional maintenance of primary human hepatocytes in vitro

AU - Xiang, Chengang

AU - Du, Yuanyuan

AU - Meng, Gaofan

AU - Soon Yi, Liew

AU - Sun, Shicheng

AU - Song, Nan

AU - Zhang, Xiaonan

AU - Xiao, Yiwei

AU - Wang, Jie

AU - Yi, Zhigang

AU - Liu, Yifang

AU - Xie, Bingqing

AU - Wu, Min

AU - Shu, Jun

AU - Sun, Da

AU - Jia, Jun

AU - Liang, Zhen

AU - Sun, Dong

AU - Huang, Yanxiang

AU - Shi, Yan

AU - Xu, Jun

AU - Lu, Fengmin

AU - Li, Cheng

AU - Xiang, Kuanhui

AU - Yuan, Zhenghong

AU - Lu, Shichun

AU - Deng, Hongkui

PY - 2019/4/26

Y1 - 2019/4/26

N2 - The maintenance of terminally differentiated cells, especially hepatocytes, in vitro has proven challenging. Here we demonstrated the long-term in vitro maintenance of primary human hepatocytes (PHHs) by modulating cell signaling pathways with a combination of five chemicals (5C). 5C-cultured PHHs showed global gene expression profiles and hepatocyte-specific functions resembling those of freshly isolated counterparts. Furthermore, these cells efficiently recapitulated the entire course of hepatitis B virus (HBV) infection over 4 weeks with the production of infectious viral particles and formation of HBV covalently closed circular DNA. Our study demonstrates that, with a chemical approach, functional maintenance of PHHs supports long-term HBV infection in vitro, providing an efficient platform for investigating HBV cell biology and antiviral drug screening.

AB - The maintenance of terminally differentiated cells, especially hepatocytes, in vitro has proven challenging. Here we demonstrated the long-term in vitro maintenance of primary human hepatocytes (PHHs) by modulating cell signaling pathways with a combination of five chemicals (5C). 5C-cultured PHHs showed global gene expression profiles and hepatocyte-specific functions resembling those of freshly isolated counterparts. Furthermore, these cells efficiently recapitulated the entire course of hepatitis B virus (HBV) infection over 4 weeks with the production of infectious viral particles and formation of HBV covalently closed circular DNA. Our study demonstrates that, with a chemical approach, functional maintenance of PHHs supports long-term HBV infection in vitro, providing an efficient platform for investigating HBV cell biology and antiviral drug screening.

KW - Antiviral Agents/isolation & purification

KW - DNA, Circular/biosynthesis

KW - DNA, Viral/biosynthesis

KW - Drug Evaluation, Preclinical

KW - Hepatitis B virus/drug effects

KW - Hepatocytes/drug effects

KW - Humans

KW - Primary Cell Culture/methods

KW - Transcriptome

KW - Virion/drug effects

KW - Virus Cultivation/methods

UR - http://www.scopus.com/inward/record.url?scp=85065415956&partnerID=8YFLogxK

U2 - 10.1126/science.aau7307

DO - 10.1126/science.aau7307

M3 - Review article

C2 - 31023926

SN - 1095-9203

VL - 364

SP - 399

EP - 402

JO - Science

JF - Science

IS - 6438

ER -

Long-term functional maintenance of primary human hepatocytes in vitro

Abstract

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