Recapitulation of SARS-CoV-2 Infection and Cholangiocyte Damage with Human Liver Organoids

Bing Zhao; Chao Ni; Ran Gao; Yuyan Wang; Li Yang; Jinsong Wei; Ting Lv; Jianqing Liang; Qisheng Zhang; Wei Xu; Youhua Xie; Xiaoyue Wang; Zhenghong Yuan; Junbo Liang; Rong Zhang; Xinhua Lin

ACE2+ cholangiocytes are preserved in human liver ductal organoid cultures. 88 To establish the SARS-CoV-2 infection model with human liver ductal organoids, 89 we first determined whether the long-term organoid culture could preserve the 90 ACE2+ cholangiocytes ex vivo. We processed single-cell RNA sequencing (scRNA-seq) 91 to interrogate the transcriptome of cholangiocytes in human liver ductal organoids. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.16.990317 doi: bioRxiv preprint 109 We next examined the susceptibility of human liver ductal organoids to 110 SARS-CoV-2. We isolated and plaque-purified the SARS-CoV-2 from a COVID-19 111 patient in Shanghai. The liver ductal organoids from two individuals were inoculated 112 with SARS-CoV-2 for 1 hour then re-embedded in Matrigel and maintained in culture Statistical analysis. 249 We employed Student's t-test or ANOVA test to analyze the parametric 250 experimental results. Significant differences were noted with asterisks. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.16.990317 doi: bioRxiv preprint The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.16.990317 doi: bioRxiv preprint The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.16.990317 doi: bioRxiv preprint The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.16.990317 doi: bioRxiv preprint