Lung transcriptome sequencing anlysis in Male Sprague-Dawley rats
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE158832 | GEO | 2020/10/01
REPOSITORIES: GEO
Similar Datasets
Project description:Respiratory failure in COVID-19 is characterized by widespread disruption of the lung’s alveolar gas exchange interface. To elucidate determinants of alveolar lung damage, we performed epithelial and immune cell profiling in lungs from 24 COVID-19 autopsies and 43 uninfected organ donors ages 18-92 years. We found marked loss of type 2 alveolar epithelial (T2AE) cells and increased peri-alveolar lymphocyte cytotoxicity in all fatal COVID-19 cases, even at early stages before typical patterns of acute lung injury are histologically apparent. In lungs from uninfected organ donors, there is also progressive loss of T2AE with increasing age which may increase susceptibility to COVID-19 mediated lung damage in older individuals. In the fatal COVID-19 cases, macrophage infiltration differed according to the histopathological pattern of lung injury. In cases with acute lung injury, we found accumulation of CD4+ macrophages that express distinctly high levels of T-cell activation and co-stimulation genes and strongly correlate with increased extent of alveolar epithelial cell depletion and CD8 T-cell cytotoxicity. Together, our results show that T2AE deficiency may underlie age-related COVID-19 risk and initiate alveolar dysfunction shortly after infection; and we define immune cell mediators that may contribute to alveolar injury in distinct pathological stages of fatal COVID-19.
2022-04-19 | GSE200988 | GEO
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
Project description:<p>SARS-CoV-2 infection causes severe pulmonary manifestations, with poorly understood mechanisms and limited treatment options. Hyperferritinemia and disrupted lung iron homeostasis in COVID-19 patients imply that ferroptosis, an iron-dependent cell death, may occur. Immunostaining and lipidomic analysis in COVID-19 lung autopsies reveal increases in ferroptosis markers, including transferrin receptor 1 and malondialdehyde accumulation in fatal cases. COVID-19 lungs display dysregulation of lipids involved in metabolism and ferroptosis. We find increased ferritin light chain associated with severe COVID-19 lung pathology. Iron overload promotes ferroptosis in both primary cells and cancerous lung epithelial cells. In addition, ferroptosis markers strongly correlate with lung injury severity in a COVID-19 lung disease model using male Syrian hamsters. These results reveal a role for ferroptosis in COVID-19 pulmonary disease; pharmacological ferroptosis inhibition may serve as an adjuvant therapy to prevent lung damage during SARS-CoV-2 infection.</p>
2024-07-11 | MTBLS3107 | MetaboLights
Project description:Lung transplantation can potentially be a life-saving treatment for patients with non-resolving COVID-19-associated respiratory failure. Concerns limiting transplant include recurrence of SARS-CoV-2 infection in the allograft, technical challenges imposed by viral-mediated injury to the native lung, and potential risk for allograft infection by pathogens associated with ventilator-associated pneumonia in the native lung. Most importantly, the native lung might recover, resulting in long-term outcomes preferable to transplant. Here, we report results of the first successful lung transplantation procedures in patients with non-resolving COVID-19-associated respiratory failure in the United States. We performed sm-FISH to detect both positive and negative strands of SARS-CoV-2 RNA in the explanted lung tissue, extracellular matrix imaging using SHIELD tissue clearance, and single cell RNA-Seq on explant and warm post-mortem lung biopsies from patients who died from severe COVID-19 pneumonia. Lungs from patients with prolonged COVID-19 were free of virus but pathology showed extensive evidence of injury and fibrosis which resembled end-stage pulmonary fibrosis. We used a machine learning approach to project single cell RNA-Seq data from patients with late stage COVID-19 onto a single cell atlas of pulmonary fibrosis, revealing similarities across cell lineages. There was no recurrence of SARS-CoV-2 or pathogens associated with pre-transplant ventilator associated pneumonias following transplantation. Our findings suggest that some patients with severe COVID-19 develop fibrotic lung disease for which lung transplantation is the only option for survival.
2020-10-28 | GSE158127 | GEO
Project description:Hyperinflammation contributes to lung injury and subsequent acute respiratory distress syndrome (ARDS) with high mortality in severe COVID-19. To understand the underlying mechanisms, we investigated the role of the lung-specific immune response. Here we profiled lymphocytes and myeloid cells in the bronchoalveolar lavage (BAL) fluid and blood of COVID-19 patients. By tracking T cell clones across tissues, we identified clonally expanded tissue-resident memory-like Th17 cells (Trm17 cells) in the lung even after viral clearance. These Trm17 cells are characterized by a potentially pathogenic cytokine profile with expression of IL17A and CSF2 (GM-CSF). Interactome analysis revealed that Trm17 cells interact with macrophages and cytotoxic CD8+ T cells, which have been associated with disease severity and lung damage. High IL-17A and GM-CSF protein levels in the serum of COVID-19 patients correlated with severe clinical course. This study suggests pulmonary Trm17 cells as one of the orchestrators of the hyperinflammation in severe COVID-19 and that these cells and their cytokines, such as GM-CSF, are promising biomarkers and potential targets for a COVID-19 therapy.
2021-02-20 | GSE167118 | GEO
Project description:Patients often present with kidney injury in COVID-19. Although severe COVID-19 cases are treated with baricitinib, a JAK inhibitor, the effects of baricitinib on the kidneys in COVID-19 are unclear. The authors examined the pharmacological effects of baricitinib on kidney injury using an in vivo murine COVID-19 model.
2024-04-18 | GSE249303 | GEO
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
Project description:Acute respiratory distress syndrome (ARDS) is a severe critical condition with a high mortality that is currently in focus given that it is associated with mortality caused by coronavirus induced disease 2019 (COVID-19). Neutrophils play a key role in the lung injury characteristic of non-COVID-19 ARDS and there is also accumulating evidence of neutrophil mediated lung injury in patients who succumb to infection with SARS-CoV-2. We undertook a functional proteomic and metabolomic survey of circulating neutrophil populations, comparing patients with COVID-19 ARDS and non-COVID-19 ARDS to understand the molecular basis of neutrophil dysregulation. Expansion of the circulating neutrophil compartment and the presence of activated low and normal density mature and immature neutrophil populations occurs in ARDS, irrespective of cause. Release of neutrophil granule proteins, neutrophil activation of the clotting cascade and upregulation of the Mac-1 platelet binding complex with formation of neutrophil platelet aggregates is exaggerated in COVID-19 ARDS. Importantly, activation of components of the neutrophil type I interferon responses is seen in ARDS following infection with SARS-CoV-2, with associated rewiring of neutrophil metabolism to promote glutamine utilisation, and the upregulation of antigen processing and presentation. Whilst dexamethasone treatment constricts the immature low density neutrophil population it does not impact upon prothrombotic hyperinflammatory neutrophil signatures.
2021-02-03 | PXD023834 | Pride
Project description:Severe coronavirus disease 2019 (COVID-19) infection may lead to lung injury, multi-organ failure, and eventually death. Cytokine storm due to excess cytokine production has been associated with fatality in severe infections. However, the specific molecular signatures associated with the elevated immune response are yet to be elucidated. We performed a mass-spectrometry-based proteomic and metabolomic analysis of COVID-19 plasma samples collected at two time points. Using Orbitrap Fusion LC-MS/MS-based label-free proteomic analysis, we identified around 10 significant proteins, 32 significant peptides, and 5 metabolites that were dysregulated at the severe time points. Few of these proteins identified by quantitative proteomics were validated using the multiple reaction monitoring (MRM) assay. Integrated pathway analysis using distinct proteomic and metabolomic signatures revealed alterations in complement and coagulation cascade, platelet aggregation, myeloid leukocyte activation pathway, and arginine metabolism. Further, we highlight the role of leukocyte activation and arginine metabolism in COVID-19 pathogenesis and targeting these pathways for COVID-19 therapeutics.
2022-01-18 | MTBLS2469 | MetaboLights
Project description:In USA, approximately 50,000 people are diagnosed with idiopathic pulmonary fibrosis (IPF) annually; and almost 40,000 of them die. IPF is a condition in which an injury to the lung leads to accumulation of scar tissue. This fibrotic tissue impairs the lungs’ ability to absorb necessary amount of oxygen. The exact etiology of IPF is unknown, but recent evidence suggests that the distal small airways (those having a diameter of less than 2mm) play a role in the early pathogenesis of IPF. Pathologic features of IPF include increased collagen deposition, the collapse of distal small airways, and the buildup of fibroblast/myofibroblast cells. Many of these features are also observed in the lungs of patients following COVID-19 infection. IPF patients who suffer from infection by COVID-19 have poor clinical outcomes and may require a lung transplant due to a significant increase in fibrotic tissue following the illness. This study aimed to investigate possible mechanisms that contribute to worsening lung fibrosis in IPF patients after being diagnosed with COVID-19. Small airway cell cultures derived from IPF and post-COVID-19 IPF patient transplant tissues along with normal lungs were submitted for RNA-sequencing and subsequent differential gene expression analysis. It has been observed that TGFB pathway is activated upon lung injury or illness, signalling profibrotic cascade. Thus, while culturing small airways ,fraction of cells were treated with TGFB.
2023-11-02 | GSE225549 | GEO