Mast cell heterogeneity in human nasal polyps
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ABSTRACT:
PROVIDER: PRJNA1171812 | ENA |
REPOSITORIES: ENA
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Project description:Mast cells (MCs) expressing a distinctive protease phenotype (MCTs) selectively expand within the epithelium of human mucosal tissues during type 2 (T2) inflammation. While MCTs are phenotypically distinct from subepithelial MCs (MCTCs), signals driving human MCT differentiation and this subset’s contribution to inflammation remain unexplored. Here, we identify TGF-b as a key driver of the MCT transcriptome in nasal polyps. We find that short-term TGF-b signaling alters MC cell surface receptor expression and partially recapitulates the in vivo MCT transcriptome, while TGF-β signaling during MC differentiation upregulates a larger number of MCT-associated transcripts and inhibits the hallmark MCTC proteases chymase and cathepsin G at both the transcript and protein level, allowing selective in vitro differentiation of MCTs for functional study. We identify discrete differences in effector phenotype between in vitro-derived MCTs and MCTCs, with MCTs greatly enhancing pro-inflammatory lipid mediator generation while selectively modifying cytokine, chemokine, and growth factor production in response to both innate and adaptive stimuli, recapitulating functional features of their tissue-associated counterpart MC subsets. Thus, our findings support a role for TGF-β in promoting human MCT differentiation and identify a discrete contribution of this cell type to T2 inflammation.
2024-11-01 | GSE279289 | GEO
Project description:Objective: We sought to obtain detailed information about transcriptional differences in epithelial cells and immune cell subsets present in polyps of aspirin-exacerbated respiratory disease and chronic rhinosinusitis with nasal polyps. Methods: After enrichment for various immune subsets by flow cytometric sorting of polyp-derived cells, we performed transcriptomic profiling by employing single-cell RNA sequencing of all patients. Results: Transcriptomic profiling revealed that epithelial and mast cells not only complement one another in terms of gene expression associated with the 15-lipoxygenase pathway, but also show a clear type 2 associated inflammatory phenotype as identified by the upregulation of POSTN, CCL26 and IL13 in patients with aspirin-exacerbated respiratory disease.
2022-04-20 | GSE196169 | GEO
Project description:Chronic rhinosinusitis with nasal polyps is a hallmaerk disease in the field of upper airway immunity and chronic inflammation. Diverse inflammatory patterns between nasal polyps have been described in patients that hail from disparate racial and geographic backgrounds. However, it remains unclear whether these immunologic differences in nasal polyps between racial groups are driven by unique molecular mechanisms. We interrogated the gene expression profiles of nasal polyp tissues from Western (United States) and East Asian (Japan) descent, compared to ethmoid sinus tissue controls.
2021-12-15 | GSE179265 | GEO
Project description:Chronic rhinosinusitis with nasal polyps is a hallmaerk disease in the field of upper airway immunity and chronic inflammation. Diverse inflammatory patterns between nasal polyps have been described in patients that hail from disparate racial and geographic backgrounds. However, it remains unclear whether these immunologic differences in nasal polyps between racial groups are driven by unique molecular mechanisms. We interrogated the gene expression profiles of nasal polyp tissues from Western (United States) and East Asian (Japan) descent, compared to ethmoid sinus tissue controls.
2021-12-15 | GSE179268 | GEO
Project description:Background: Alternative polyadenylation (APA) is emerging as a widespread mechanism of gene regulation. The usage of APA sites allows a single gene to encode multiple mRNA transcripts with different 3'-untranslated region (3'UTR) lengths. Many disease processes reflect the importance of the regulation of APA site switching. The objective of this study was to explore the profiling of tandem APA sites in nasal polyps compared with nasal uncinate process mucosa. Methods: Sequencing of APA sites (SAPAS) based on second-generation sequencing technology was undertaken to investigate the use of tandem APA sites and identify gene expression patterns in samples from the nasal polyps and nasal uncinate process mucosa of two patients with chronic rhinosinusitis with nasal polyps. The findings of the SAPAS analysis were validated via quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Results: First, the results showed a switching of 3'UTR lengths in nasal polyps compared with nasal uncinate process mucosa. From the two patients, 105 overlapping genes in the nasal polyps were switched to distal poly(A) sites, and 90 such genes were switched to proximal poly(A) sites. Several Gene Ontology terms were enriched in the list of genes with switched APA sites, including transcription regulation, cell cycle, apoptosis, and metabolism. Second, we detected genes that showed differential expression with at least a 3-fold difference between nasal polyp tissue and nasal uncinate process mucosa. Between the two sample types, 627 genes exhibited differential expression. The qRT-PCR results confirmed our SAPAS results. Conclusion: APA site-switching events of 3'UTRs are prevalent in nasal polyp tissue, and the regulation of gene expression mediated by APA may play an important role in the formation and persistence of nasal polyps. Our results may provide new insights into the possible pathophysiologic processes involved in nasal polyps.
2012-12-31 | GSE39957 | GEO
Project description:Background: Alternative polyadenylation (APA) is emerging as a widespread mechanism of gene regulation. The usage of APA sites allows a single gene to encode multiple mRNA transcripts with different 3'-untranslated region (3'UTR) lengths. Many disease processes reflect the importance of the regulation of APA site switching. The objective of this study was to explore the profiling of tandem APA sites in nasal polyps compared with nasal uncinate process mucosa. Methods: Sequencing of APA sites (SAPAS) based on second-generation sequencing technology was undertaken to investigate the use of tandem APA sites and identify gene expression patterns in samples from the nasal polyps and nasal uncinate process mucosa of two patients with chronic rhinosinusitis with nasal polyps. The findings of the SAPAS analysis were validated via quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Results: First, the results showed a switching of 3'UTR lengths in nasal polyps compared with nasal uncinate process mucosa. From the two patients, 105 overlapping genes in the nasal polyps were switched to distal poly(A) sites, and 90 such genes were switched to proximal poly(A) sites. Several Gene Ontology terms were enriched in the list of genes with switched APA sites, including transcription regulation, cell cycle, apoptosis, and metabolism. Second, we detected genes that showed differential expression with at least a 3-fold difference between nasal polyp tissue and nasal uncinate process mucosa. Between the two sample types, 627 genes exhibited differential expression. The qRT-PCR results confirmed our SAPAS results. Conclusion: APA site-switching events of 3'UTRs are prevalent in nasal polyp tissue, and the regulation of gene expression mediated by APA may play an important role in the formation and persistence of nasal polyps. Our results may provide new insights into the possible pathophysiologic processes involved in nasal polyps. Investigate the use of tandem APA sites of 3'ends of mRNAs using second-generation sequencing technology.
2012-12-31 | E-GEOD-39957 | biostudies-arrayexpress
Project description:Patients with chronic rhinosinusitis (CRS) have abnormal immune responses triggered by a variety of infectious agents, airborne toxins and fungi. Respiratory epithelial cells serve as relay stations capable of amplifying or augmenting cues received from external stimuli to nearby immune cells located in the sinus mucosa. Previous studies have identified increases in complement components and complement gene expression in the mucosa of patients with atopic CRS with nasal polyps (CRSwNP). As part of a larger study, we used shotgun proteomics to quantify changes in mucus proteins between patients with and without nasal polyps.
2016-05-26 | PXD004144 | Pride
Project description:Asthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP) is a common disruptive eosinophilic disease. Therefore, we sought to identify gene expression changes in nasosinus inflamed mucosa and adjacent polyp tissue from subjects with aCRSwNP. Twelve asthmatic chronic rhinosinusitis (aCRS) subjects (11 with nasal polyps; aCRSwNP) provided inflamed nasosinus mucosa (11 samples) and adjacent polyp (10 samples) or a small mixed mucosa and polyp specimen (1 sample) (thus, 22 samples overall). Inflamed mucosa or polyp was from the middle meatus or anterior ethmoid cavity. As control samples, nasosinus tissue was collected from the inferior turbinate or uncinate process from normal or rhinitis subjects without nasal polyps (n=17); 4 had physician-diagnosed allergic rhinitis (AR), 2 had suspected AR, 1 had suspected vasomotor rhinitis, and 10 had no signs of nasosinus disease, allergy, or atopy. All 4 AR subjects chose to donate tissue outside of their known allergy season(s).
2010-08-12 | E-GEOD-23552 | biostudies-arrayexpress
Project description:Asthmatic chronic rhinosinusitis with nasal polyps (aCRSwNP) is a common disruptive eosinophilic disease. Therefore, we sought to identify gene expression changes in nasosinus inflamed mucosa and adjacent polyp tissue from subjects with aCRSwNP.
2010-08-12 | GSE23552 | GEO
Project description:Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by a chronic inflammatory process often associated with comorbid asthma. In this study, we analysed the transcriptomes of single T helper (Th) cells from nasal polyps of patients with CRS and validated these findings using multiparameter flow cytometry. Polyp tissue contained suppressive Treg and Th2 cells, type 2 innate lymphoid cells (ILC2) and 3 transcriptionally distinct subsets of cytotoxic CD4 T cells (CD4 CTL). GATA3 expression was a feature of polyp Treg while Th2 cells highly expressed TCN1, CD200R, HPGDS and were enriched for genes involved in lipid metabolism. Only a portion of polyp Th2 cells expressed the prostaglandin D2 receptor CRTH2, while a subpopulation of CD109+CRTH2- Th2 cells expressed mRNA for common inhibitor receptors and produced IL-10. Taken together, we resolve the complexity of T helper cells in CRSwNP patients to identify several distinct clusters of CD4 CTL and a population of CD109+CRTH2- Th2 cells with putative regulatory potential.
2021-07-02 | GSE179292 | GEO