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| Status |
Public on Oct 01, 2023 |
| Title |
hPSC-derived Airway Organoids-based Screen Reveals the Role of HIF1/Glycolysis Axis in SARS-CoV-2 Infection [bulk RNA-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
SARS-CoV-2, the virus causing recently pandemic, primarily infects the respiratory tract. There is an urgent need to develop platforms using disease relevant human cells to dissect the molecular mechanism regulating SARS-CoV-2 infection and perform drug screen. Here, we derived airway organoids from human pluripotent stem cells (hPSC-AO). The hPSC-AOs, particularly ciliated cells, express ACE2 and are permissive to SARS-CoV-2 infection. Using hPSC-AOs, we performed a high content screen and identified GW6471, which blocks SARS-CoV-2 infection. RNA-seq analysis suggested that GW6471 blocking SARS-CoV-2 infection by inhibiting HIF1α, which is further validated by chemotin, another HIF1α inhibitor. Furthermore, metabolic profiling identified that the downregulation of glycolysis upon GW6471 treatment, which is further validated by RNA-seq. Finally, xanthohumol, a prenylated flavonoid suppressing fatty acid and cholesterol biosynthesis, blocks SARS-CoV-2 infection. Together, we applied the high content screen, RNA-seq and metabolic profiling to define the key role of HIF1α-glycolysis axis in SARS-CoV-2 infection, which provides a target pathway for anti-viral drug development.
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| Overall design |
HPSCs derived airway organoids (AOs) or colonic organoids (COs) were treated with control or 10 uM GW6471 in the presence of SARS-CoV-2 infection.
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| Contributor(s) |
Duan X, Chen S, Zhang T |
| Citation missing |
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| Submission date |
Oct 27, 2020 |
| Last update date |
Oct 01, 2023 |
| Contact name |
Shuibing Chen |
| E-mail(s) |
shuibing.chen@gmail.com
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| Phone |
2127465431
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| Organization name |
Weill Cornell Medical College
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| Department |
Surgery
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| Street address |
A 827B, 1300 York Ave
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| City |
New York |
| State/province |
NY |
| ZIP/Postal code |
10065 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (15)
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| This SubSeries is part of SuperSeries: |
| GSE160232 |
hPSC-derived Airway Organoids-based Screen Reveals the Role of HIF1/Glycolysis Axis in SARS-CoV-2 Infection. |
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| Relations |
| BioProject |
PRJNA672685 |
| SRA |
SRP288855 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE160230_raw_counts.hPSC_AO.downsample.txt.gz |
470.5 Kb |
(ftp)(http) |
TXT |
| GSE160230_raw_counts.hPSC_AO.txt.gz |
494.2 Kb |
(ftp)(http) |
TXT |
| GSE160230_raw_counts.hPSC_CO.txt.gz |
376.9 Kb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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