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A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection [CUT&RUN]

ABSTRACT: A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection [CUT&RUN]

PROVIDER: PRJNA837898 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR19197503_1.fastq.gz	Fastqsanger.gz
	SRR19197503_2.fastq.gz	Fastqsanger.gz
	SRR19197504_1.fastq.gz	Fastqsanger.gz
	SRR19197504_2.fastq.gz	Fastqsanger.gz
	SRR19197505_1.fastq.gz	Fastqsanger.gz

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A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection [CUT&RUN]

Project description: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.

2022-12-07 | GSE202966 | GEO

A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection [ATAC-seq]

2022-12-07 | GSE202965 | GEO

A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection [scRNA-seq]

2022-12-07 | GSE202964 | GEO

A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection [bulk RNA-seq]

2022-12-07 | GSE202963 | GEO

A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection.

Project description:A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection.

| PRJNA837892 | ENA

A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection [scRNA-seq]

Project description:A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection [scRNA-seq]

| PRJNA837899 | ENA

A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection [ATAC-seq]

Project description:A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection [ATAC-seq]

| PRJNA837901 | ENA

A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection [bulk RNA-seq]

Project description:A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection [bulk RNA-seq]

| PRJNA837900 | ENA

A multi-organoid platform identifies CIART as a key factor for SARS-CoV-2 infection.

Project description:COVID-19 is a systemic disease involving multiple organs. We previously established a platform to derive organoids and cells from human pluripotent stem cells to model SARS-CoV-2 infection and perform drug screens1,2. This provided insight into cellular tropism and the 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 multiplicities of infection for lung airway organoids, lung alveolar organoids and cardiomyocytes, and identified several genes that are generally implicated in controlling SARS-CoV-2 infection, including CIART, the circadian-associated repressor of transcription. Lung airway organoids, lung alveolar organoids and cardiomyocytes derived from isogenic CIART-/- human pluripotent stem cells were significantly resistant to SARS-CoV-2 infection, independently of viral entry. Single-cell RNA-sequencing analysis further validated the decreased levels of SARS-CoV-2 infection in ciliated-like cells of lung airway organoids. CUT&RUN, ATAC-seq and RNA-sequencing analyses showed that CIART controls SARS-CoV-2 infection at least in part through the regulation of NR4A1, a gene also identified from the multi-organoid analysis. Finally, transcriptional profiling and pharmacological inhibition led to the discovery that the Retinoid X Receptor pathway regulates SARS-CoV-2 infection downstream of CIART and NR4A1. The multi-organoid platform identified the role of circadian-clock regulation in SARS-CoV-2 infection, which provides potential therapeutic targets for protection against COVID-19 across organ systems.

| S-EPMC10014579 | biostudies-literature

A Multi-Organoid Platform Identifies CIART as a Key Factor for SARS-CoV-2 Infection.

Project description:This SuperSeries is composed of the SubSeries listed below.

2022-12-07 | GSE202967 | GEO