Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

SARS-CoV-2 infection of Lung Organoids Reveals Conserved Use of Tetraspanin-8 by Ancestral-, Delta-, and Omicron- Variants

ABSTRACT: Ancestral SARS coronavirus-2 (SARS-CoV-2) and variants of concern (VOC) caused a global pandemic with a spectrum of disease variation linked to immune dysfunction. The mechanistic underpinnings of variation related to lung epithelium are relatively understudied. Here, we biobanked lung organoids by preserving stem cell function. We optimized viral infection with H1N1 swine flu and next comprehensively characterized epithelial responses to SARS-CoV-2 infection in phenotypically stable lung organoids from twenty different subjects. We discovered Tetraspanin 8 (TSPAN8) as a novel mediator of SARS-CoV-2-infection. TSPAN8 facilitates SARS-CoV-2 infection rates but does not via enhanced ACE-2-mediated entry. In head-to-head comparisons with Ancestral SARS-CoV-2, Delta- and Omicron- VOC displayed lower overall infection rates of organoids but triggered increased epithelial interferon responses. All variants shared highest tropism for ciliated- and goblet- cells. ACE2- and TSPAN8- expression are universal features of infected cells. TSPAN8-blocking antibodies diminish SARS-CoV-2 infection and may spur novel avenues for COVID-19 therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE211562 | GEO | 2022/09/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcriptome profiling of the lungs of K18-hACE2 mice infected with SARS-CoV-2 wild-type strain or beta variant

Project description:Diverse severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have emerged since the beginning of COVID-19 pandemic. We investigated the immunological and pathological characteristics of SARS-CoV-2 beta variant of concern (VOC) compared to the ancestral strain. To investigate a broad spectrum of immunological responses and to determine the underlying mechanisms of differentially expressed cytokines, we analyzed the whole transcriptome of lung homogenates from SARS-CoV-2 ancestral strain- and beta variant-infected mice at 4 and 6 dpi.

2022-08-17 | GSE202998 | GEO

RNAseq analyses in HEK293T-ACE2 cells infected with SARS-CoV-2 (VOC Delta, 24hours) vs untreated cells

Project description:In this study a gene expression (i.e., RNAseq) analysis was performed in HEK293T-ACE2 cellular model upon infection with viral particle belonging to VOC Delta (MOI: 0.026) for 24 hours in order to have a global picture of the transcriptome landscape in response to early phase of infection of SARS-CoV-2 ( VOC Delta infection and to evaluate the role of Ca2+ in HEK293-ACE2 cellular model and transfer to homeostasis in SARS-COV-2 patients (by Pasqualino de Antonellis1-2* and Veronica Ferrucci 1-2* (first authors) et al. and Massimo Zollo1-2# (corresponding author). Manuscript in preparation 2022 July 15th 2022. Short title "ATP2B1 (PMCA1), regulated by FOXO3, influences susceptibility to severe COVID19".

2022-12-01 | E-MTAB-11973 | biostudies-arrayexpress

RNA-Seq investigating the global landscape of the host molecular response to infection by SARS-CoV-2 variants of concern

Project description:Purpose: RNA-Seq was performed for gene expression analysis following infection of human cells with different VOC depending on the experiment group to investigate changes in the host and viral molecular response. Methods: RNA was extracted from 10^6 cells using the Qiagen RNeasy extraction kit according to the manufacturer's protocol and quantified by nanodrop. Samples were submitted for RNA-Seq to Genewiz (Azenta) for library preparation and subsequent steps. Results: We have identified SARS-CoV-2 VOC-specific differences in RNA expression, including for N, Orf9b, and Orf6. We have also measured ISG expression and proinflammatory gene suppression across the VOC, determining changes in ISG expression and proinflammatory gene suppression during amongst VOC during SARS-CoV-2 evolution. Conclusions: Our study examines changes in the host molecular response to VOC infection to identify changes in gene expression, especially those related to the innate immune response, that have occurred during SARS-CoV-2 evolution.

2023-09-20 | GSE213759 | GEO

An Airway Organoid-Based Screen Identifies a Role for the HIF1α-Glycolysis Axis in SARS-CoV-2 Infection

Project description:SARS-CoV-2 causes the COVID-19 pandemic. It is urgent to develop disease models to dissect mechanisms regulating SARS-CoV-2 infection. Here, we derive airway organoids from human pluripotent stem cells (hPSC-AOs). The hPSC-AOs, particularly ciliated-like cells, are permissive to SARS-CoV-2 infection. Using this platform, we perform a high content screen and identify GW6471, which blocks SARS-CoV-2 infection. GW6471 can also block infection of the B.1.351 SARS-CoV-2 variant. RNA-seq analysis suggests that GW6471 blocks SARS-CoV-2 infection at least in part by inhibiting HIF1α, which is further validated by chemical inhibitor and genetic perturbation targeting HIF1α. Metabolic profiling identifies decreased rates of glycolysis upon GW6471 treatment, consistent with transcriptome profiling. Finally, xanthohumol, 5-(Tetradecyloxy)-2-furoic acid, and ND-646, three compounds that suppress fatty acid biosynthesis, also block SARS-CoV-2 infection. Together, a high content screen coupled with transcriptome and metabolic profiling reveals a key role of the HIF1α-glycolysis axis in mediating SARS-CoV-2 infection of human airway epithelium.

2021-09-24 | ST001921 | MetabolomicsWorkbench

SARS-CoV-2 infection of human embryonic stem cell-derived lung organoids

Project description:RNA-seq for SARS-CoV-2 infection of human embryonic stem cell-derived lung organoids

2023-08-05 | GSE155717 | GEO

A Platform to Define Cellular Targets of SARS-COV-2 Infection Using Human Pluripotent Stem Cell-Derived Cells and Organoids

Project description:The SARS-CoV-2 virus has already caused over a million COVID-19 cases and over fifty-thousand deaths globally. There is an urgent need to create novel models to study SARS-CoV-2 virus using human disease-relevant cells and tissues to understand key features of virus biology. We present a platform comprised of nine different cell and organoid derivatives from human pluripotent stem cells (hPSCs) representing all three primary germ layers, including lung progenitors and alveolar type II (AT2) cells, pancreatic endocrine cells, liver organoids, endothelial cells, cardiomyocytes, macrophages, microglia, and both cortical and dopaminergic neurons. We systematically probed which cell types are permissive to SARS-CoV-2 infection. Human pancreatic beta cells and hepatocytes were strikingly permissive to SARS-CoV-2 infection, further validated using adult primary human islets and liver organoids. Both in vitro and in a humanized mouse model, human lung progenitors and AT2 cells express the ACE2 viral receptor and were highly permissive to SARS-CoV-2 infection. Transcriptomic analysis following SARS-CoV-2 infection of hPSC-derived pancreatic and lung organoids revealed upregulation of chemokines but not type I/III interferon signaling, similar to what was seen in primary human COVID-19 pulmonary infection. Therefore, hPSC-derived cells phenocopy human COVID-19 disease and provide a valuable resource to understand SARS-CoV-2 biology and search for novel therapeutics.

2020-06-11 | GSE147903 | GEO

Identification of Lead Drug Candidates for COVID-19 based on Drug Screening Using Human Pluripotent Stem Cell-Derived Cells/Organoids

Project description:We systematically probed which cell types are permissive to SARS-CoV-2 infection. Transcriptomic analysis following SARS-CoV-2 infection of hPSC-derived lung organoids revealed upregulation of chemokines but not type I/III interferon signaling, similar to what was seen in primary human COVID-19 pulmonary infection.

2021-01-01 | GSE148697 | GEO

Identification of Lead Drug Candidates for COVID-19 based on Drug Screening Using Human Pluripotent Stem Cell-Derived Cells/Organoids

Project description:We systematically probed which cell types are permissive to SARS-CoV-2 infection. Transcriptomic analysis following SARS-CoV-2 infection of hPSC-derived pancreatic and lung organoids revealed upregulation of chemokines but not type I/III interferon signaling, similar to what was seen in primary human COVID-19 pulmonary infection.

2020-06-12 | GSE151803 | GEO

Organoid modeling of lung-resident immune responses to SARS-CoV-2 infection

Project description:We sought to understand the effect of SARS-CoV-2 infection on transcriptomes of human lung organoids at various time points during infection.

2023-08-08 | GSE230398 | GEO

The respective roles of TMPRSS2 and cathepsins for SARS-CoV-2 infection in human respiratory organoids

Project description:A critical aspect of the mechanism of SARS-CoV-2 infection is the protease-mediated activation of the viral spike (S) protein. The type II transmembrane serine protease TMPRSS2 is crucial for SARS-CoV-2 infection in lung epithelial Calu-3 cells and murine airways. However, the importance of TMPRSS2 needs to be re-examined because the ability to utilize TMPRSS2 is significantly reduced in the Omicron variants that spread globally. For this purpose, replication profiles of SARS-CoV-2 were analyzed in human respiratory organoids. All tested viruses, including Omicron variants, replicated efficiently in these organoids. Notably, all SARS-CoV-2 strains retained replication ability in TMPRSS2-gene knockout (KO) respiratory organoids, suggesting that TMPRSS2 is not essential for SARS-CoV-2 infection in human respiratory tissues. However, TMPRSS2-gene knockout significantly reduces the inhibitory effect of nafamostat, suggesting the advantage of TMPRSS2-utilizing ability for the SARS-CoV-2 infection in these organoids. Interestingly, Omicron variants regained the TMPRSS2-utilizing ability in recent subvariants. The basal infectivity would be supported mainly by cathepsins because the cathepsin inhibitor, EST, showed a significant inhibitory effect on infection with any SARS-CoV-2 strains, mainly when used with nafamostat. A supplementary contribution of other serine proteases was also suggested because the infection of the Delta variant was still inhibited partially by nafamostat in TMPRSS2 KO organoids. Thus, various proteases, including TMPRSS2, other serine proteases, and cathepsins, co-operatively contribute to SARS-CoV-2 infection significantly in the respiratory organoids. Thus, SARS-CoV-2 infection in the human respiratory tissues would be more complex than observed in cell lines or mice.

2024-11-20 | GSE279753 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data