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| Status |
Public on Dec 07, 2022 |
| Title |
A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection [ATAC-seq] |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
COVID-19 is a systemic disease involving multiple organs. Human pluripotent stem cells (hPSCs) derived organoids/cells provide insight into cellular tropism and host response, yet the molecular mechanisms regulating SARS-CoV-2 infection remain poorly defined. Here, we systematically examined changes in transcript profiles caused by SARS-CoV-2 infection at different MOIs for airway organoids (AWOs), alveolar organoids (ALOs) and cardiomyocytes (CMs), and identified several genes, including CIART, that are generally implicated in controlling SARS-CoV-2 infection. AWOs, ALOs, and CMs derived from isogenic CIART-/- hPSCs were significantly resistant to SARS-CoV-2 infection, independent of viral entry. Single-cell RNA-seq further validated the decreased levels of SARS-CoV-2 infection in multi-ciliated cells of AWOs. CUT&RUN, ATAC-seq and RNA-seq analyses found that CIART controls SARS-CoV-2 infection at least in part through regulating NR4A1, a gene also identified from the multi-organoid analysis. Finally, transcriptional profiling and pharmacological inhibition revealed that the Retinoid X Receptor (RXR) pathway regulates SARS-CoV-2 infection downstream of CIART/NR4A1. The multi-organoid platform provides potential therapeutic targets for protection against COVID-19 across organ systems.
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| Overall design |
WT and CIART-/- human pluripotentstem cells were differentiated into cardiomyocytes and used for ATAC-seq analysis.
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| Contributor(s) |
Tang X, Xue D, Zhang T, Chen S |
| Citation(s) |
36918693 |
| |
| Submission date |
May 13, 2022 |
| Last update date |
Jul 14, 2023 |
| Contact name |
Shuibing Chen |
| E-mail(s) |
shuibing.chen@gmail.com
|
| Phone |
2127465431
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| Organization name |
Weill Cornell Medical College
|
| Department |
Surgery
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| Street address |
A 827B, 1300 York Ave
|
| 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 (6)
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| This SubSeries is part of SuperSeries: |
| GSE202967 |
A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection. |
|
| Relations |
| BioProject |
PRJNA837901 |
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