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Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection

Xiaoqiang Chai, Longfei Hu, Yan Zhang, Weiyu Han, Zhou Lu, Aiwu Ke, Jian Zhou, Guoming Shi, Nan Fang, Jia Fan, Jiabin Cai, Jue Fan, Fei Lan
doi: https://doi.org/10.1101/2020.02.03.931766
Xiaoqiang Chai
1Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University
2Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
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Longfei Hu
3Singleron Biotechnologies, Yaogu Avenue 11, Nanjing, Jiangsu, China
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Yan Zhang
3Singleron Biotechnologies, Yaogu Avenue 11, Nanjing, Jiangsu, China
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Weiyu Han
1Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University
2Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
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Zhou Lu
1Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University
2Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
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Aiwu Ke
1Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University
2Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
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Jian Zhou
1Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University
2Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
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Guoming Shi
1Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University
2Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
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Nan Fang
3Singleron Biotechnologies, Yaogu Avenue 11, Nanjing, Jiangsu, China
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Jia Fan
1Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University
2Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
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Jiabin Cai
1Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University
2Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
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  • For correspondence: cai.jiabin@zs-hospital.sh.cn fanjue@singleronbio.com fei_lan@fudan.edu.cn
Jue Fan
3Singleron Biotechnologies, Yaogu Avenue 11, Nanjing, Jiangsu, China
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  • For correspondence: cai.jiabin@zs-hospital.sh.cn fanjue@singleronbio.com fei_lan@fudan.edu.cn
Fei Lan
1Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University
2Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Key Laboratory of Medical Epigenetics and Metabolism, Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
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  • For correspondence: cai.jiabin@zs-hospital.sh.cn fanjue@singleronbio.com fei_lan@fudan.edu.cn
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Abstract

A newly identified coronavirus, 2019-nCoV, has been posing significant threats to public health since December 2019. ACE2, the host cell receptor for severe acute respiratory syndrome coronavirus (SARS), has recently been demonstrated in mediating 2019-nCoV infection. Interestingly, besides the respiratory system, substantial proportion of SARS and 2019-nCoV patients showed signs of various degrees of liver damage, the mechanism and implication of which have not yet been determined. Here, we performed an unbiased evaluation of cell type specific expression of ACE2 in healthy liver tissues using single cell RNA-seq data of two independent cohorts, and identified specific expression in cholangiocytes. The results indicated that virus might directly bind to ACE2 positive cholangiocytes but not necessarily hepatocytes. This finding suggested the liver abnormalities of SARS and 2019-nCoV patients may not be due to hepatocyte damage, but cholangiocyte dysfunction and other causes such as drug induced and systemic inflammatory response induced liver injury. Our findings indicate that special care of liver dysfunction should be installed in treating 2019-nCoV patients during the hospitalization and shortly after cure.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 04, 2020.
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Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection
Xiaoqiang Chai, Longfei Hu, Yan Zhang, Weiyu Han, Zhou Lu, Aiwu Ke, Jian Zhou, Guoming Shi, Nan Fang, Jia Fan, Jiabin Cai, Jue Fan, Fei Lan
bioRxiv 2020.02.03.931766; doi: https://doi.org/10.1101/2020.02.03.931766
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Specific ACE2 Expression in Cholangiocytes May Cause Liver Damage After 2019-nCoV Infection
Xiaoqiang Chai, Longfei Hu, Yan Zhang, Weiyu Han, Zhou Lu, Aiwu Ke, Jian Zhou, Guoming Shi, Nan Fang, Jia Fan, Jiabin Cai, Jue Fan, Fei Lan
bioRxiv 2020.02.03.931766; doi: https://doi.org/10.1101/2020.02.03.931766

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