Project description:Intra-tracheal instillation of saline or PM2.5 was performed in BALB/c Mice once a week for consecutive eight weeks. Genomewide transcriptome profiling of coding genes, long non-coding RNAs (lncRNA), and circular RNAs (circRNA) in mice lung were done by ribosomal RNA-depleted RNA sequencing.
Project description:Purpose: Tracheal epithelial brush cells are rare chemosensory cells defined by their expression of elements of the bitter taste transduction system, and known to activate the cholinergic nervous system in the murine lung. Similar chemosensory cells in the intestine can generate lipid mediators and pro-inflammatory cytokines but whether brush cell can contribute to airway inflammation is unknown. Furthermore, despite the advances in understanding chemosensory cell effector functions, the receptors that mediate chemosensory cell activation and expansion beyond taste receptors in any compartment remain largely unknown. Methods: In this study, we isolated tracheal brush cells by FACS from naïve ChATBAC-eGFP mice with knockin of eGFP within a BAC spanning the acetylcholine transferase locus, marking brush cells in the epithelium and performed transcriptome profiling using low input RNA sequencing. We compared tracheal brush cells to EpCAM+ epithelial cells and CD45+ hematopoetic cells in naive mice. Results: When compared to EpCAM+ EpCs and to CD45+ cells in the airway, principal component analysis demonstrated that brush cells grouped quite distinctly. This brush cell distinction relative to EpCAM+ cells, was further reflected in the striking number of highly differentially expressed genes. This included 1305 genes expressed at 4-fold or higher levels in EpCAM+eGFP+ cells (brush cells), of which 418 genes were expressed at 32-fold or higher levels in brush cells. Conclusions: Our study represents the first detailed analysis of the transcriptome of tracheal brush cells and identifies a unique set of genes that are primarily expressed in brush cells including the bitter taste transduction system, synthenic machinery for several pro-inflammatory lipid mediators and HoxA2 transciptional factors.
Project description:Whole transcriptome sequencing was performed on blood samples collected from patients with benign tracheal stenosis and normal controls. To explore the possible biological functions of the differentially expressed genes in patients with benign tracheal stenosis, and to provide a valuable molecular basis for investigating the pathogenesis of benign tracheal stenosis.
Project description:We have sampled several tumour regions from a single ccRCC patient after 6 weeks everolimus treatment, including both primary and metastatic site samples to investigate intra-tumour heterogeneity.
Project description:<p>Progressive lung function decline is a hallmark of chronic obstructive pulmonary disease (COPD). Airway dysbiosis occurs in COPD, but whether it contributes to disease progression remains unknown. Here we showed, through a longitudinal analysis on two cohorts involving four UK centers, that baseline airway dysbiosis in COPD patients, characterized by enrichment of opportunistic pathogenic taxa, was associated with rapid forced expiratory volume in one second (FEV1) decline over two years. The dysbiosis was associated with exacerbation-related FEV1 fall and sudden FEV1 fall at stability, contributing to long-term FEV1 decline. The microbiota- FEV1-decline association was validated in a third cohort in China. Human multi-omics and murine studies showed that airway Staphylococcus aureus colonization promoted lung function decline through homocysteine, which elicited a neutrophil apoptosis-to-NETosis shift via AKT1-S100A8/A9 axis. S. aureus depletion via bacteriophages restored lung function in emphysema mice, providing a fresh approach to slow COPD progression by targeting airway microbiome.</p><p><br></p><p><strong>Linked studies:</strong></p><p><strong>UPLC-MS/MS assays</strong> of murine samples are reported in this study.</p><p><strong>UPLC-MS/MS assays</strong> of human samples are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS5423' rel='noopener noreferrer' target='_blank'>MTBLS5423</a>.</p><p><strong>UPLC-MS/MS assays</strong> of original cohort human samples are reported in <a href='https://www.ebi.ac.uk/metabolights/MTBLS4017' rel='noopener noreferrer' target='_blank'>MTBLS4017</a>.</p>
Project description:Tracheal aspirate (TAs) samples were collected from intubated preterm infants with hemodynamically significant intracardiac shunt (ICS), and a diagnosis of ICS-BPD/ICS-BPD-PH. 36 TA samples were analyzed. Small RNAs were extracted and the expression miRNAs was detected with PCR arrays.
Project description:DNA methylation profile of mouse sperm from conventionally-raised mice and gut dysbiosis experienced mice were characterized using whole-genome bisulfite sequencing. Genome-wide DNA methylation changes between control and dysbiotic male�s sperm were highly comparable, with no change in DNAme globally or at genomic features, only 21 differentially methylated regions (DMR) were identified, which did not overlap known regulatory elements. Epididymal sperm samples were harvested from 11 weeks old inbred male mice that were experiencing gut microbiota dysbiosis for 6-week (antibiotics treated, n=5), or drink sterilized water (control, n=5).