RT Journal Article
SR Electronic
T1 Recapitulation of SARS-CoV-2 Infection and Cholangiocyte Damage with Human Liver Organoids
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.03.16.990317
DO 10.1101/2020.03.16.990317
A1 Bing Zhao
A1 Chao Ni
A1 Ran Gao
A1 Yuyan Wang
A1 Li Yang
A1 Jinsong Wei
A1 Ting Lv
A1 Jianqing Liang
A1 Qisheng Zhang
A1 Wei Xu
A1 Youhua Xie
A1 Xiaoyue Wang
A1 Zhenghong Yuan
A1 Junbo Liang
A1 Rong Zhang
A1 Xinhua Lin
YR 2020
UL http://biorxiv.org/content/early/2020/03/17/2020.03.16.990317.abstract
AB The newly emerged pandemic coronavirus, SARS-CoV-2, has posed a significant public health threat worldwide. However, the mode of virus transmission and tissue tropism is not well established yet. Recent findings of substantial liver damage in patients and ACE2+ cholangiocytes in healthy liver tissues prompted us to hypothesize that human liver ductal organoids could serve as a model to determine the susceptibility and mechanisms underlining the liver damage upon SARS-CoV-2 infection. By single-cell RNA sequencing, we found that long-term liver ductal organoid culture preserved the human specific ACE2+ population of cholangiocytes. Moreover, human liver ductal organoids were permissive to SARS-CoV-2 infection and support robust replication. Notably, virus infection impaired the barrier and bile acid transporting functions of cholangiocytes through dysregulation of genes involved in tight junction formation and bile acid transportation, which could explain the bile acid accumulation and consequent liver damage in patients. These results indicate that control of liver damage caused directly by viral infection should be valued in treating COVID-19 patients. Our findings also provide an application of human organoids in investigating the tropism and pathogenesis of SARS-CoV-2, which would facilitate novel drug discovery.