Submitted by Shuibing Chen (Weill Cornell Medical College, USA) on Aug 10 2020
Platform: ngs – Illumina NovaSeq 6000 (Homo sapiens)
Pubmed: 33116299
Summary The SARS-CoV-2 has already caused over twelve million COVID-19 cases and half a million deaths worldwide. There is an urgent need to create novel models using human disease-relevant cells to study SARS-CoV-2 biology and to facilitate drug screening. As SARS-CoV-2 primarily infects the respiratory tract, we developed a lung organoid model using human pluripotent stem cells (hPSC-LOs) that could be adapted for drug screening. The hPSC-LOs, particularly alveolar type II-like cells, express the viral entry receptor ACE2, are permissive to SARS-CoV-2 infection, and showed robust induction of chemokines and cytokines upon SARS-CoV-2 infection, similar to what is seen in COVID-19 patients. Nearly 25% of these patients have gastrointestinal manifestations, which are associated with worse COVID-19 outcomes1. We therefore also generated complementary hPSC-derived colonic organoids (hPSC-COs) to explore the response of colonic cells to SARS-CoV-2 infection. We found that multiple colonic cell types, especially enterocytes, express ACE2 and are permissive to SARS-CoV-2 infection. Using hPSC-LOs, we performed a high throughput screen of FDA-approved drugs and identified entry inhibitors of SARS-CoV-2, including imatinib, mycophenolic acid (MPA), and quinacrine dihydrochloride (QNHC). Pre- or post-infection treatment at physiologically relevant levels of these drugs significantly inhibited SARS-CoV-2 infection of both hPSC-LOs and hPSC-COs. Together, these data demonstrate that hPSC-LOs and hPSC-COs infected by SARS-CoV-2 can serve as disease models to study SARS-CoV-2 infection and provide a valuable resource for drug screening to identify candidate COVID-19 therapeutics.
ID | Title | Cell Type | Timepoint | Reported Virus | Virus Species | Exclusion Reason |
---|---|---|---|---|---|---|
GSM4697982 | Healthy Lung autopsy [Healthy-lung] | lung | Healthy | Uninfected | ||
GSM4697983 | Healthy Lung autopsy_1 [HealthyLungBiopsy_1] | lung | Healthy | Uninfected | ||
GSM4697984 | Healthy Lung autopsy_2 [HealthyLungBiopsy_2] | lung | Healthy | Uninfected | ||
GSM4697985 | COVID_19 lung autopsy_1 [COVI19-Lung_59L-H1] | lung | COVID-19 | Severe acute respiratory syndrome-related coronavirus | Data failed QCpseudoaligned_reads is 843792 (low number of usable reads) |
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GSM4697986 | COVID_19 lung autopsy_2 [COVI19-Lung_62L-H2] | lung | COVID-19 | Severe acute respiratory syndrome-related coronavirus | ||
GSM4697987 | COVID_19 lung autopsy_3 [COVI19-Lung_64L-H3] | lung | COVID-19 | Severe acute respiratory syndrome-related coronavirus | ||
GSM4697988 | hPSC_Lung organoid_mock_1 [2A] | lung | Healthy | Uninfected | ||
GSM4697989 | hPSC_Lung organoid_mock_2 [2B] | lung | Healthy | Uninfected | ||
GSM4697990 | hPSC_Lung organoid_mock_3 [2C] | lung | Healthy | Uninfected | ||
GSM4697991 | hPSC_Lung organoid_SARS-CoV-2_1 [2D] | lung | COVID-19 | Severe acute respiratory syndrome-related coronavirus | ||
GSM4697992 | hPSC_Lung organoid_SARS-CoV-2_2 [2E] | lung | COVID-19 | Severe acute respiratory syndrome-related coronavirus | ||
GSM4697993 | hPSC_Lung organoid_SARS-CoV-2_3 [2F] | lung | COVID-19 | Severe acute respiratory syndrome-related coronavirus | ||
GSM4718728 | hPSC_Lung organoid_SARS-CoV-2_DMSO_1 [LungOrganoid-DMSO-1] | lung | COVID-19 | Severe acute respiratory syndrome-related coronavirus | ||
GSM4718729 | hPSC_Lung organoid_SARS-CoV-2_DMSO_2 [LungOrganoid-DMSO-2] | lung | COVID-19 | Severe acute respiratory syndrome-related coronavirus | ||
GSM4718730 | hPSC_Lung organoid_SARS-CoV-2_DMSO_3 [LungOrganoid-DMSO-3] | lung | COVID-19 | Severe acute respiratory syndrome-related coronavirus | ||
GSM4718731 | hPSC_Lung organoid_SARS-CoV-2_imatinib_1 [LungOrganoid-10uM-Imatinib-1] | lung | COVID-19 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Imatinib treated |
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GSM4718732 | hPSC_Lung organoid_SARS-CoV-2_imatinib_2 [LungOrganoid-10uM-Imatinib-2] | lung | COVID-19 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Imatinib treated |
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GSM4718733 | hPSC_Lung organoid_SARS-CoV-2_imatinib_3 [LungOrganoid-10uM-Imatinib-3] | lung | COVID-19 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Imatinib treated |