Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Organotypic Human Lung Bud Microarrays Identify BMP-dependent SARS-CoV-2 Infection in Lung Cells

ABSTRACT: Although lung disease is the primary clinical outcome in COVID-19 patients, how SARS-CoV-2 induces lung pathology remains elusive. Here we describe a high-throughput platform to generate self-organizing ad commensurate human lung buds derived from hESCs cultured on micropatterned substrates. Lung buds resemble human fetal lungs and display proximo-distal patterning of alveolar and airway tissue directed by KGF. These lung buds are susceptible to infection by SARS-CoV-2 and endemic coronaviruses and can be used to track cell type-specific cytopathic effects in hundreds of lung buds in parallel. Transcriptomic comparisons of infected lung buds and postmortem tissue of COVID-19 patients identified an induction of BMP signaling pathway. BMP activity renders lung cells more susceptible to SARS-CoV-2 infection and its pharmacological inhibition impairs infection by this virus. These data highlight the rapid and scalable access to disease-relevant tissue using lung buds that recapitulate key features of human lung morphogenesis and viral infection biology.

ORGANISM(S): Homo sapiens

PROVIDER: GSE225564 | GEO | 2023/02/21

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Self-organized stem cell-derived human lung buds with proximo-distal patterning and novel targets of SARS-CoV-2

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the global COVID-19 pandemic and the lack of therapeutics hinders pandemic control. Although lung disease is the primary clinical outcome in COVID-19 patients, how SARS-CoV-2 induces tissue pathology in the lung remains elusive. Here we describe a high-throughput-based platform to generate tens of thousands of self-organizing, nearly identical, and genetically matched human lung buds derived from human pluripotent stem cells (hPSCs) cultured on confined geometries on micropattern chips. Strikingly, in vitro-derived human lung buds resemble fetal human lung tissue and display in vivo-like proximo-distal coordination of alveolar and airway tissue differentiation whose 3D epithelial self-organization is directed by the levels of KGF. Single-cell transcriptomics unveiled the cell identities and ontogeny of airway and alveolar tissue and the specification of WNThi cycling alveolar stem cells from alveolar progenitors. These synthetic human lung buds are susceptible to SARS-CoV-2 infection and can be used to track cell type-dependent susceptibilities to infection, intercellular transmission and cytopathology in airway and alveolar tissue in individual synthetic lung buds. We detected an increased susceptibility to infection in alveolar cells and identified cycling alveolar stem cells as targets of SARS-CoV-2. We used this platform to test neutralizing antibodies isolated from convalescent plasma that efficiently blocked SARS-CoV-2 infection and intercellular transmission. Our platform offers unlimited, rapid and scalable access to disease-relevant lung tissue that recapitulate human lung development and can be used to track SARS-CoV-2 infection and identify pre-clinical candidate therapeutics for COVID-19.

2021-12-21 | GSE163698 | GEO

Senescent endothelial cells are predisposed to SARS-CoV-2 infection and subsequent endothelial dysfunction

Project description:The coronavirus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), remains to spread worldwide. COVID-19 is characterized by the striking high mortality in elderly; however, its mechanistic insights remain unclear. Systemic thrombosis has been highlighted in the pathogenesis of COVID-19, and lung microangiopathy in association with endothelial cells (ECs) injury has been reported by post-mortem analysis of the lungs. Here, we experimentally investigated the SARS-CoV-2 infection in cultured human ECs, and performed a comparative analysis for post-infection molecular events using early passage and replicative senescent ECs. We found that; 1) SARS-CoV-2 infects ECs but does not replicate and disappears in 72 hours without causing severe cell damage, 2) Senescent ECs are highly susceptible to SARS-CoV-2 infection, 3) SARS-CoV-2 infection alters various genes expression, which could cause EC dysfunctions, 4) More genes expression is affected in senescent ECs by SARS-CoV-2 infection than in early passage ECs, which might causes further exacerbated dysfunction in senescent ECs. These data suggest that sustained EC dysfunctions due to SARS-CoV-2 infection may contribute to the microangiopathy in the lungs, leading to deteriorated inflammation and thrombosis in COVID-19. Our data also suggest a possible causative role of EC senescence in the aggravated disease in elder COVID-19 patients.

2023-05-01 | GSE206677 | GEO

ACE2 knockout hinders SARS-CoV-2 propagation in iPS cell-derived airway and alveolar epithelial cells

Project description:Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, continues to spread around the world with serious cases and deaths. It has also been suggested that different genetic variants in the human genome affect both the susceptibility to infection and severity of disease in COVID-19 patients. Angiotensin-converting enzyme 2 (ACE2) has been identified as a cell surface receptor for SARS-CoV and SARS-CoV-2 entry into cells. The construction of an experimental model system using human iPS cells would enable further studies of the association between viral characteristics and genetic variants. Airway and alveolar epithelial cells are cell types of the lung that express high levels of ACE2 and are suitable for in vitro infection experiments. Here, we show that human iPS cell-derived airway and alveolar epithelial cells are highly susceptible to viral infection of SARS-CoV-2. Using gene knockout with CRISPR-Cas9 in human iPS cells we demonstrate that ACE2 plays an essential role in the airway and alveolar epithelial cell entry of SARS-CoV-2 in vitro. Replication of SARS-CoV-2 was strongly suppressed in ACE2 knockout (KO) lung cells. Our model system based on human iPS cell-derived lung cells may be applied to understand the molecular biology regulating viral respiratory infection leading to potential therapeutic developments for COVID-19 and the prevention of future pandemics.

2024-08-21 | GSE275240 | GEO

Genome wide expression from COVID-19 patients and controls' lung

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to coronavirus disease 2019 (Covid-19) which has caused worldwide pandemic infection. Yet due to unknown reason, certain COVID-19 patients exhibit severe inflammatory reactions associated with cytokine storm and neutrophil infiltration and neutrophil extracellular traps (NETs) in the lung, leading to further complications of SARS-CoV-2 infection. To find out whether the cause of lung injury in COVID-19 patients is due to increased reactive oxygen species and subsequently NET formation we have compared the post-mortem lung biopsies of deceased COVID-19 patients to normal lung tissues using RNA-Seq analysis.

2023-01-31 | GSE208076 | GEO

Human cardiac pericytes are susceptible to SARS-CoV-2 infection

Project description:Coronavirus disease 2019 (COVID-19) is associated with serious cardiovascular complications, including myocarditis, thrombosis, and dysregulated hemodynamic responses. The mechanism(s) underlying these disease manifestations are incompletely understood. Given a critical role for pericytes in supporting endothelial cell health and maintaining vascular integrity, we hypothesized that infection of pericytes could explain some of the cardiovascular complications of COVID-19. Here, we present evidence of SARS-CoV-2 infection in cardiac pericytes in patients with COVID-19 myocarditis. We show that cardiac pericytes are permissive to SARS-CoV-2 infection in organotypic slice and primary cell cultures. SARS-CoV-2 enters cardiac pericytes through an ACE2 and endosomal-dependent mechanism. Consequences of cardiac pericyte infection include upregulation of inflammatory chemokine and cytokine expression, type I interferon signaling, mediators of endothelial constriction, and cell death. Collectively, these data demonstrate that human cardiac pericytes are susceptible to SARS-CoV-2 infection and suggest a possible role for pericyte infection in the pathogenesis of COVID-19.

2022-08-31 | GSE183850 | GEO

CYP19A1 mediated sex hormone metabolism promotes severe disease outcome in SARS-CoV-2 infected male golden hamsters

Project description:Male sex belongs to one of the risk factors for severe COVID-19 outcome. However, underlying mechanisms that could affect sex dependent disease outcome are yet unknown. Here, we identified the CYP19A1 gene encoding for the testosterone-to-estradiol metabolizing enzyme CYP19A1 (alias aromatase) as a host factor that contributes to worsened disease outcome in male hamsters. SARS-CoV-2 infection increases CYP19A1 transcription most prominently in the lungs of male animals, which correlates with reduced circulating testosterone and increased circulating estradiol levels. Dysregulated sex hormone levels in male golden hamsters are associated with reduced lung function compared to females. Treatment of SARS-CoV-2 infected hamsters with letrozole, a clinically approved CYP19A1 inhibitor, supported recovery of dysregulated sex hormone levels and was associated with improved lung function in male but not female animals compared to placebo controls. Whole-lung transcriptome analysis in letrozole treated versus placebo treated control groups revealed key pathways associated with improved lung health in males. To seek translation of these findings into humans, we analyzed autopsy-derived lung samples of COVID-19 cases from three independent study sites. We found that CYP19A1 transcription and protein expression is strongly elevated in the lungs of men who died with COVID-19 as compared to females or non-COVID-19 controls. Our findings highlight the role of the lung as a yet unrecognized but critical organ involved in metabolic responses against respiratory virus infections. Furthermore, inhibition of CYP19A1 by the clinically approved drug letrozole may pose a new therapeutic strategy to reduce poor long-term COVID-19 outcome.

2022-01-21 | E-MTAB-11162 | biostudies-arrayexpress

Linear epitope-specific IgG responses to SARS-CoV-2 and related human coronaviruses in human COVID-19 convalescent sera

Project description:The on-going COVID-19 pandemic requires a deeper understanding of the long-term antibody responses that persist following SARS-CoV-2 infection. To that end, we determined epitope-specific IgG antibody responses in COVID-19 convalescent sera collected at 5 months post-diagnosis and compared that to sera from naïve individuals. Each serum sample was reacted with a high-density peptide microarray representing the complete proteome of SARS-CoV-2 as 15 mer peptides with 11 amino acid overlap and homologs of spike glycoprotein, nucleoprotein, membrane protein, and envelope small membrane protein from related human coronaviruses. Binding signatures were compared between COVID-19 convalescent patients and naïve individuals using the web service tool EPIphany.

2022-02-05 | E-MTAB-10740 | biostudies-arrayexpress

Attenuation of SARS-CoV-2 Infection by Losartan in Human Kidney Organoids

Project description:COVID-19 associated acute kidney injury (COVID-AKI) is a common complication of SARS-CoV-2 infection in hospitalized patients. It is unclear how susceptible human kidneys are to direct SARS-CoV-2 infection and whether pharmacologic manipulation of the renin-angiotensin II signaling (RAS) pathway modulates this susceptibility. Using induced pluripotent stem cell derived kidney organoids, SARS-CoV-1, SARS-CoV-2 and MERS-CoV tropism, defined by the paired expression of a host receptor (ACE2, NRP1 or DPP4) and protease (TMPRSS2, TMPRSS4, FURIN, CTSB or CTSL), was identified primarily amongst proximal tubule cells. Losartan, an angiotensin II receptor blocker being tested in COVID-19 patients, inhibited angiotensin II mediated internalization of ACE2, upregulated interferon stimulated genes (IFITM1 and BST2) known to restrict viral entry, and attenuated the infection of proximal tubule cells by SARS-CoV-2. Our work highlights the susceptibility of proximal tubule cells to SARS-CoV-2 and reveals a putative protective role for RAS inhibitors during SARS-CoV-2 infection.

2022-01-23 | GSE149687 | GEO

SARS-CoV-2 infection of primary human lung epithelium for COVID-19 modeling and drug discovery

Project description:Coronavirus disease 2019 (COVID-19) is the latest respiratory pandemic resulting from zoonotic transmission of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). Severe symptoms include viral pneumonia secondary to infection and inflammation of the lower respiratory tract, in some cases causing death. We developed primary human lung epithelial infection models to understand responses of proximal and distal lung epithelium to SARS-CoV-2 infection. Differentiated air-liquid interface cultures of proximal airway epithelium and 3D organoid cultures of alveolar epithelium were readily infected by SARS-CoV-2 leading to an epithelial cell-autonomous proinflammatory response. We validated the efficacy of selected candidate COVID-19 drugs confirming that Remdesivir strongly suppressed viral infection/replication. We provide a relevant platform for studying COVID-19 pathobiology and for rapid drug screening against SARS-CoV-2 and future emergent respiratory pathogens.

2020-11-06 | GSE155518 | GEO

bulk RNAseq of SARS-COV2 infected human lung organoid

Project description:Coronavirus disease 2019 (COVID-19) is the latest respiratory pandemic resulting from zoonotic transmission of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). Severe symptoms include viral pneumonia secondary to infection and inflammation of the lower respiratory tract, in some cases causing death. We developed primary human lung epithelial 5 infection models to understand responses of proximal and distal lung epithelium to SARS-CoV-2 infection. Differentiated air-liquid interface cultures of proximal airway epithelium and 3D organoid cultures of alveolar epithelium were readily infected by SARS-CoV-2 leading to an epithelial cell-autonomous proinflammatory response. We validated the efficacy of selected candidate COVID-19 drugs confirming that Remdesivir strongly suppressed viral 10 infection/replication. We provide a relevant platform for studying COVID-19 pathobiology and for rapid drug screening against SARS-CoV-2 and future emergent respiratory pathogens.

2020-11-06 | GSE160435 | 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