Age-related STAT3 signaling regulates severity of respiratory syncytial viral infection in human bronchial epithelium cells
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ABSTRACT:
PROVIDER: PRJNA1013318 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25918584_1.fastq.gz | Fastqsanger.gz | |||
| SRR25918584_2.fastq.gz | Fastqsanger.gz | |||
| SRR25918585_1.fastq.gz | Fastqsanger.gz | |||
| SRR25918585_2.fastq.gz | Fastqsanger.gz | |||
| SRR25918586_1.fastq.gz | Fastqsanger.gz |
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Project description:Respiratory syncytial virus (RSV) causes severe disease mostly in infants; however, mechanisms of age association remain elusive. Here, employing human bronchial epithelium models generated from tracheal aspirate-derived basal stem cells of neonates and adults, we investigate whether age regulates RSV-epithelium interaction to determine disease severity. We show that following RSV infection, only neonatal epithelium model exhibits cytopathy and mucus hyperplasia, and neonatal epithelium has more robust viral spread and inflammatory responses than adult epithelium. Mechanistically, RSV-infected neonatal ciliated cells display age-related impairment of STAT3 activation, rendering susceptibility to apoptosis, which facilitates viral spread. In contrast, SARS-CoV-2 infection of ciliated cells has no effect on STAT3 activation and is not affected by age. Taken together, our findings identify an age-related and RSV-specific interaction with neonatal bronchial epithelium that critically contributes to severity of infection, and STAT3 activation offers a potential strategy to battle severe RSV disease in infants.
2024-09-01 | GSE242397 | GEO
Project description:Respiratory syncytial virus (RSV) selectively targets ciliated cells in human bronchial epithelium and can cause bronchiolitis and pneumonia mostly in infants. To identify molecular targets of intervention during RSV infection in infants, we investigate how age regulates RSV interaction with the bronchial epithelium barrier. Employing precision-cut lung slices and air-liquid interface cultures generated from infant and adult human donors, we found robust RSV virus spread and extensive apoptotic cell death only in infant bronchial epithelium. In contrast, adult bronchial epithelium showed insignificant barrier damage and limited RSV infection. Single nuclear RNA-sequencing revealed age-related insufficiency of an anti-apoptotic STAT3 activation response to RSV infection in infant ciliated cells, which was exploited to facilitate virus spread via the extruded apoptotic ciliated cells carrying RSV. Activation of STAT3 and blockade of apoptosis rendered protection against severe RSV infection in infant bronchial epithelium. Lastly, apoptotic inhibitor treatment of a neonatal mouse model of RSV infection ameliorated infection and inflammation in the lung. Taken together, our findings identify a STAT3-mediated anti-apoptosis pathway as a target to battle severe RSV disease in infants.
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Project description:The main objective of CHARMACOMA is to explore the capacity of the severe asthmatic bronchial smooth muscle to modify bronchial epithelium physiology from a metabolic point of view.
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Project description:The main objective of CHARMACOMA is to explore the capacity of the severe asthmatic bronchial smooth muscle to modify bronchial epithelium physiology from a metabolic point of view.
2026-02-09 | PXD059603 | Pride
Project description:19 bronchial epithelial SAGE libraries were constructed and analyzed in this study. Discussed in the study: IDENTIFICATION OF NOVEL LUNG GENES IN BRONCHIAL EPITHELIUM BY SERIAL ANALYSIS OF GENE EXPRESSION Kim M. Lonergan1, Raj Chari1, Ronald J. deLeeuw1, Ashleen Shadeo1, Bryan Chi1, Ming-Sound Tsao2, Steven Jones3, Marco Marra3, Victor Ling1, Raymond Ng1,4, Calum MacAulay5, Stephen Lam5 and Wan L. Lam1 From the 1Department of Cancer Genetics & Developmental Biology, 5Department of Cancer Imaging, 3Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Research Centre, Vancouver, BC, Canada, 2Ontario Cancer Institute / Princess Margaret Hospital, Toronto, ON, Canada, 4the Department of Computer Science, University of British Columbia, Vancouver, BC, Canada A description of the transcriptome of human bronchial epithelium should provide a basis for studying lung diseases including cancer. We demonstrate here that minute epithelial specimens obtained by bronchial brushings afford reliable profiling by serial analysis of gene expression (SAGE) leading to lung gene discovery. We have deduced global gene expression profiles of bronchial epithelium and lung parenchyma, based upon a vast data set of nearly two million sequence tags from 21 SAGE libraries generated from individuals with a history of smoking. Cluster and linear regression analysis demonstrate the repeatability and reproducibility of bronchial SAGE libraries, and suggest that the transcriptome of the bronchial epithelium is distinct from that of lung parenchyma and other tissue types. This distinction is highlighted by the abundant expression of signature genes that reflect tissue-specific and region-specific functions. Through our analysis we have identified novel bronchial-enriched genes and a novel transcript variant for surfactant, pulmonary-associated protein B in lung parenchyma. Conspicuously, gene expression associated with ciliogenesis is evident in bronchial epithelium. Additionally, it is noted that a large number of unmapped tags awaits further investigation. This study represents a comprehensive delineation of the bronchial and parenchyma transcriptomes, identifying more than 20,000 known and hypothetical genes expressed in the human lung, constituting one of the largest human SAGE studies reported to date. Keywords: bronchial epithelium 19 bronchial epithelial SAGE libraries were constructed and analyzed in this study.
2006-07-14 | E-GEOD-3707 | biostudies-arrayexpress
Project description:19 bronchial epithelial SAGE libraries were constructed and analyzed in this study. Discussed in the study: IDENTIFICATION OF NOVEL LUNG GENES IN BRONCHIAL EPITHELIUM BY SERIAL ANALYSIS OF GENE EXPRESSION Kim M. Lonergan1, Raj Chari1, Ronald J. deLeeuw1, Ashleen Shadeo1, Bryan Chi1, Ming-Sound Tsao2, Steven Jones3, Marco Marra3, Victor Ling1, Raymond Ng1,4, Calum MacAulay5, Stephen Lam5 and Wan L. Lam1 From the 1Department of Cancer Genetics & Developmental Biology, 5Department of Cancer Imaging, 3Canada's Michael Smith Genome Sciences Centre, British Columbia Cancer Research Centre, Vancouver, BC, Canada, 2Ontario Cancer Institute / Princess Margaret Hospital, Toronto, ON, Canada, 4the Department of Computer Science, University of British Columbia, Vancouver, BC, Canada A description of the transcriptome of human bronchial epithelium should provide a basis for studying lung diseases including cancer. We demonstrate here that minute epithelial specimens obtained by bronchial brushings afford reliable profiling by serial analysis of gene expression (SAGE) leading to lung gene discovery. We have deduced global gene expression profiles of bronchial epithelium and lung parenchyma, based upon a vast data set of nearly two million sequence tags from 21 SAGE libraries generated from individuals with a history of smoking. Cluster and linear regression analysis demonstrate the repeatability and reproducibility of bronchial SAGE libraries, and suggest that the transcriptome of the bronchial epithelium is distinct from that of lung parenchyma and other tissue types. This distinction is highlighted by the abundant expression of signature genes that reflect tissue-specific and region-specific functions. Through our analysis we have identified novel bronchial-enriched genes and a novel transcript variant for surfactant, pulmonary-associated protein B in lung parenchyma. Conspicuously, gene expression associated with ciliogenesis is evident in bronchial epithelium. Additionally, it is noted that a large number of unmapped tags awaits further investigation. This study represents a comprehensive delineation of the bronchial and parenchyma transcriptomes, identifying more than 20,000 known and hypothetical genes expressed in the human lung, constituting one of the largest human SAGE studies reported to date. Keywords: bronchial epithelium
2006-07-14 | GSE3707 | GEO
Project description:Transcriptional profiling of hyperplastic, metaplastic, and dysplastic lesions of the bronchus in comparison with normal bronchial epithelium. The aim was to identify transcripts and cell signalling pathways associated with the development of isolated premalignant lesions and/or lesions combined with each other in the same bronchial epithelium.
2016-05-25 | GSE81819 | GEO
Project description:The COVID-19 pandemic has revealed differences in individual susceptibility and severity, with pre-existing respiratory diseases as potential risk factors. Using an in vitro model of differentiated primary bronchial epithelial cells, we investigated the molecular mechanisms of SARS-CoV-2 infection in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD). Our study found that CF and COPD airway epithelium had reduced susceptibility to SARS-CoV-2 compared to healthy controls. This was linked to preserved epithelial integrity, lower viral replication, and attenuated antiviral and inflammatory responses. Mechanistically, we identified reduced TMPRSS2 activity as a contributing factor in CF epithelium. Importantly, the baseline upregulation of complement and inflammatory pathways in CF and COPD epithelium appeared to prime an antiviral state prior to infection. Analysis of a COVID-19 patient cohort validated our findings, showing correlations between specific inflammatory markers (CXCL-10, SERPINA1, and CFB) and SARS-CoV-2 infection severity. This study offers insights into SARS-CoV-2 pathogenesis and potential biomarkers for clinical monitoring.
2025-02-12 | PXD055635 | Pride
Project description:<h4><strong>BACKGROUND: </strong>Several studies have shown a correlation between an altered metabolome and respiratory allergies. The epithelial barrier hypothesis proposes that an epithelial barrier dysfunction can result in allergic diseases development. Der p 1 allergen from house dust mite is a renowned epithelial barrier disruptor and allergy initiator due to its cysteine-protease activity. Here, we compared the metabolic profile of the bronchial epithelium exposed or not to Der p 1 during barrier establishment to understand its active role in allergy development.</h4><h4><strong>METHODS: </strong>Calu-3 cells were cultivated in air-liquid interface cultures and exposed to either Der p 1 or Ole e 1 allergens during barrier establishment. The comparative metabolomics analysis of apical and basolateral media were performed using liquid chromatography and capillary electrophoresis both coupled to mass spectrometry.</h4><h4><strong>RESULTS: </strong>We showed that epithelial barrier disruption by Der p 1 was associated with a specific metabolic profile, which was highly dependent on the state of the epithelium at the time of contact. Moreover, an apical-basolateral distribution of the metabolites was also observed, indicating a compartmentalization of the response with differential metabolic patterns. A number of metabolites were changed by Der p 1, mainly related to amino acids metabolism, such as L-arginine, L-kynurenine and L-methionine.</h4><h4><strong>CONCLUSION: </strong>This work is the first report on the metabolic response in human bronchial epithelial cells associated with cysteine-protease Der p 1 activity, which could contribute to allergy development. Moreover, it supports a reformulated epithelial barrier hypothesis that might help to explain allergies and their increasing prevalence.</h4>
2023-08-22 | MTBLS1755 | MetaboLights
Project description:In this study we investigated whether there exists a genomic signature that can accurately predict the course of a respiratory syncytial virus (RSV) infection in hospitalized young infants. We used early blood microarray transcriptome profiles from 39 infants that were followed until recovery and of which the level of disease severity was determined retrospectively. Applying support vector machine learning on age by sex standardized transcriptomic data, an 84 gene signature was identified that discriminated hospitalized infants with eventually less severe RSV infection from infants that suffered from most severe RSV disease.
2016-11-11 | E-MTAB-5195 | biostudies-arrayexpress