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SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE210061 | GEO | 2022/10/04

REPOSITORIES: GEO

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SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology.

Project description:Although respiratory symptoms are the most prevalent disease manifestation of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), infection can also damage other organs, including the brain, gut, and liver. Symptoms of liver damage are observed in nearly half of patients that succumb to severe SARS-CoV-2 infection. Here we use human-induced pluripotent stem cell-derived liver organoids (HLOs) to recapitulate and characterize liver pathology following virus exposure. Utilizing single-cell sequencing technology, we identified robust transcriptomic changes that occur in SARS-CoV-2 infected liver cells as well as uninfected bystander cells. Our results show a significant induction of many inflammatory pathways, including IFN-α, INF-γ, and IL-6 signaling. Our results further identify IL-6 signaling as a potential mechanism for liver-mediated activation of circulating macrophages.

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SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology (scRNA-Seq)

Project description:Symptoms of liver damage are observed in nearly half of patients that succumb to severe SARS-CoV-2 infection. Here we use human induced pluripotent stem cell-derived liver organoids (HLOs) to recapitulate and characterize liver pathology following virus exposure. Utilizing single-cell sequencing technology, we identified robust transcriptomic changes that occur in SARS-CoV-2 infected liver cells as well as uninfected bystander cells. Our results show a significant induction of many inflammatory pathways, including IFN-α, INF-γ and IL-6 signaling. Our results further identify IL-6 signaling as a potential mechanism for liver-mediated activation of circulating macrophages.

2022-10-04 | GSE210059 | GEO

SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology (Bulk RNA-Seq)

2022-10-04 | GSE210058 | GEO

SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology

Project description:SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology

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SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology (scRNA-Seq)

Project description:SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology (scRNA-Seq)

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Protocol for SARS-CoV-2 infection of kidney organoids derived from human pluripotent stem cells.

Project description:This protocol presents the use of SARS-CoV-2 isolates to infect human kidney organoids, enabling exploration of the impact of SARS-CoV-2 infection in a human multicellular in vitro system. We detail steps to generate kidney organoids from human pluripotent stem cells (hPSCs) and emulate a diabetic milieu via organoids exposure to diabetogenic-like cell culture conditions. We further describe preparation and titration steps of SARS-CoV-2 virus stocks, their subsequent use to infect the kidney organoids, and assessment of the infection via immunofluorescence. For complete details on the use and execution of this protocol, please refer to Garreta et al. (2022).1.

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SARS-CoV-2 infection of human pluripotent stem cell-derived liver organoids reveals potential mechanisms of liver pathology (Bulk RNA-Seq)

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Human induced pluripotent stem cell-derived salivary gland organoids model SARS-CoV-2 infection and replication.

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Human Pluripotent Stem Cell-Derived Intestinal Organoids Model SARS-CoV-2 Infection Revealing a Common Epithelial Inflammatory Response.

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leading to coronavirus disease 2019 (COVID-19) usually results in respiratory disease, but extrapulmonary manifestations are of major clinical interest. Intestinal symptoms of COVID-19 are present in a significant number of patients, and include nausea, diarrhea, and viral RNA shedding in feces. Human induced pluripotent stem cell-derived intestinal organoids (HIOs) represent an inexhaustible cellular resource that could serve as a valuable tool to study SARS-CoV-2 as well as other enteric viruses that infect the intestinal epithelium. Here, we report that SARS-CoV-2 productively infects both proximally and distally patterned HIOs, leading to the release of infectious viral particles while stimulating a robust transcriptomic response, including a significant upregulation of interferon-related genes that appeared to be conserved across multiple epithelial cell types. These findings illuminate a potential inflammatory epithelial-specific signature that may contribute to both the multisystemic nature of COVID-19 as well as its highly variable clinical presentation.

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