Virus Expression Database

GSE150819

Generation of human bronchial organoids for SARS-CoV-2 research

Submitted by Daisuke Okuzaki (Osaka university, Japan) on May 19 2020

Platform: ngs – Illumina NextSeq 500 (Homo sapiens)

Pubmed: None listed

Summary Coronavirus disease 2019 (COVID-19) is a disease that causes fatal disorders including severe pneumonia. To develop a therapeutic drug for COVID-19, a model that can reproduce the viral life cycle and can evaluate the drug efficacy of anti-viral drugs is essential. In this study, we established a method to generate human bronchial organoids (hBO) from commercially available cryopreserved primary human bronchial epithelial cells (hBEpC) and examined whether they could be used as a model for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research. The hBO were found to contain basal, club, ciliated, and goblet cells. Also, angiotensin-converting enzyme 2 (ACE2), which is a receptor for SARS-CoV-2, and transmembrane serine proteinase 2 (TMPRSS2), which is an essential serine protease for priming spike protein of SARS-CoV-2, were highly expressed. After hBO were infected with SARS-CoV-2, remarkable amplification of the viral genome and the expression of spike protein of the virus was confirmed. In addition, cytotoxicity and pyknosis cells were observed due to the virus infection. Furthermore, treatment with camostat, an inhibitor of TMPRSS2, reduced the viral copy number to 2% of the control group. RNA-seq analyses revealed genes whose expression was altered by SARS-CoV-2 infection and camostat treatment. These results suggest that our hBO are acceptable for SARS-CoV-2 infection and replication, but also can be used as a model for COVID-19 drug discovery.

18 Samples

ID Title Cell Type Timepoint Reported Virus Virus Species Exclusion Reason
GSM4559193 Ctl_1: uninfected hBP_rep1 bronchial epithelial cell  uninfected Uninfected
GSM4559194 Ctl_2: uninfected hBP_rep2 bronchial epithelial cell  uninfected Uninfected
GSM4559195 Ctl_3: uninfected hBP_rep3 bronchial epithelial cell  uninfected Uninfected
GSM4559196 V_1: SARS-CoV-2_rep1 bronchial epithelial cell  5 days SARS-CoV-2 Severe acute respiratory syndrome-related coronavirus
GSM4559197 V_2: SARS-CoV-2_rep2 bronchial epithelial cell  5 days SARS-CoV-2 Severe acute respiratory syndrome-related coronavirus
GSM4559198 V_3: SARS-CoV-2_rep3 bronchial epithelial cell  5 days SARS-CoV-2 Severe acute respiratory syndrome-related coronavirus
GSM4559199 VC_1: SARS-CoV-2+camostat_rep1 bronchial epithelial cell  SARS-CoV-2 Severe acute respiratory syndrome-related coronavirus Extra interventions
camostat treated
GSM4559200 VC_2: SARS-CoV-2+camostat_rep2 bronchial epithelial cell  SARS-CoV-2 Severe acute respiratory syndrome-related coronavirus Extra interventions
camostat treated
GSM4559201 VC_3: SARS-CoV-2+camostat_rep3 bronchial epithelial cell  SARS-CoV-2 Severe acute respiratory syndrome-related coronavirus Extra interventions
camostat treated
GSM4559202 A549_1: A549_rep1 non-small cell lung adenocarcinoma cell line  [A-549 ] uninfected Uninfected
GSM4559203 A549_2: A549_rep2 non-small cell lung adenocarcinoma cell line  [A-549 ] uninfected Uninfected
GSM4559204 A549_3: A549_rep3 non-small cell lung adenocarcinoma cell line  [A-549 ] uninfected Uninfected
GSM4559205 lungNHBE_1: hBEpC_rep1 bronchial epithelial cell  uninfected Uninfected
GSM4559206 lungNHBE_2: hBEpC_rep2 bronchial epithelial cell  uninfected Uninfected
GSM4559207 lungNHBE_3: hBEpC_rep3 bronchial epithelial cell  uninfected Uninfected
GSM4559208 lungORG_1: hBO_rep1 bronchial epithelial cell  uninfected Uninfected
GSM4559209 lungORG_2: hBO_rep2 bronchial epithelial cell  uninfected Uninfected
GSM4559210 lungORG_3: hBO_rep3 bronchial epithelial cell  uninfected Uninfected