Single Cell sequencing of human bronchial Brush cells in IPF and disease controls
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PROVIDER: PRJNA595355 | ENA |
REPOSITORIES: ENA
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Project description:The study aimed to compare the gene expression profiles at a single cell level in bronchial brush cells between patients with idiopathic pulmonary fibrosis and disease controls.
2022-07-03 | GSE141939 | GEO
Project description:There is microscopic spatial and temporal heterogeneity of pathologic changes in idiopathic pulmonary fibrosis (IPF) lung tissue, which may relate to heterogeneity in pathophysiological mediators of disease and clinical progression. We measured gene expression in samples from lung biopsies or explants in order to assess relationships with pathological features and systemic biomarkers. RNA was extracted directly from lung tissue samples from 40 IPF patients or 8 healthy controls.
2014-10-14 | E-GEOD-53845 | biostudies-arrayexpress
Project description:The airway epithelium forms the interface between the inhaled environment and the lung. The airway epithelium is dysfunctional in asthma and epigenetic mechanisms are considered a contributory factor. We hypothesised that the DNA methylation profiles of cultured primary airway epithelial cells (AECs) would differ between cells isolated from individuals with asthma (n=17) versus those without asthma (n=16). AECs were isolated from patients by two different isolation techniques; pronase digestion (9 non-asthmatic, 8 asthmatic) and bronchial brushings (7 non-asthmatic and 9 asthmatic). DNA methylation was assessed using an Illumina Infinium HumanMethylation450 BeadChip array. DNA methylation of AECs clustered by isolation technique and linear regression identified 111 CpG sites differentially methylated between isolation techniques in healthy individuals. As a consequence, the effect of asthmatic status on DNA methylation was assessed within AEC samples isolated using the same technique. In pronase isolated AECs, 15 DNA regions were differentially methylated between asthmatics and non-asthmatics. In bronchial brush isolated AECs, 849 differentially methylated DNA regions were identified with no overlap to pronase regions. In conclusion, regardless of cell isolation technique, differential DNA methylation was associated with asthmatic status in AECs, providing further evidence for aberrant DNA methylation as a signature of epithelial dysfunction in asthma.
2019-10-31 | GSE137716 | GEO
Project description:Objectives: Idiopathic pulmonary fibrosis (IPF) is a complex disease in which a multitude of proteins and networks are disrupted. Interrogation of genome-wide transcription through RNA sequencing (RNA-Seq) enables the determination of genes whose differential expression is most significant in IPF, as well as the detection of alternative splicing events which are not easily observed with traditional microarray experiments. Methods: Messenger RNA extracted from 8 IPF lung samples and 7 healthy controls was sequenced on an Illumina HiSeq. Analysis of differential expression and exon usage was performed using Bioconductor packages. The gene periostin was selected for validation of alternative splicing by quantitative PCR, and pathway analysis was performed to determine enrichment for differentially expressed and spliced genes. Results: There were 873 genes differentially expressed in IPF (FDR 5%), and 440 unique genes had significant differential splicing events (FDR 5%). In particular, cassette exon 21 of the gene periostin was significantly more likely to be spliced out in IPF samples (adj pval = 2.06e-09), and this result was confirmed by qPCR (Wilcoxon pval = 3.11e-4). We also found that genes close to SNPs in the discovery set of a recent IPF GWAS were enriched for genes differentially expressed in our data, including genes like mucin5B and desmoplakin which have been previously associated with IPF. Conclusions: There is significant differential splicing and expression in IPF lung samples as compared with healthy controls. We found a strong signal of differential cassette exon usage in periostin, an extracellular matrix protein whose increased gene-level expression has been associated with IPF and its clinical progression, but for which differential splicing has not been studied in the context of IPF. Our results suggest that alternative splicing of periostin and other genes may be involved in the pathogenesis of IPF. mRNA sequencing of 8 IPF and 7 control lung tissue samples.
2014-03-27 | E-GEOD-52463 | biostudies-arrayexpress
Project description:The activated fibroblast is the central effector cell for the progressive fibrotic process that characterizes idiopathic pulmonary fibrosis (IPF). An understanding of the genomic phenotype of this cell in isolation is essential to the understanding of disease pathogenesis and is integral to strategizing therapeutic trials. Employing a unique technique that minimizes cellular phenotypic alterations, we characterized the genomic phenotype of non-cultured pulmonary fibroblasts from the lungs of patients with advanced IPF. This approach revealed several novel genes and pathways previously unreported in IPF fibroblasts. Specifically, we demonstrate altered expression in proteasomal constituents, ubiquitination mediators, the Wnt pathway and several cell cycle regulators suggestive of loss of normal cell cycle controls. The pro-inflammatory cytokine CXCL12 was also up-regulated which may provide a mechanism for fibrocytes’ recruitment, while up-regulated oncogenic KIT may promote fibroblast over proliferation. Paradoxically, pro-apoptotic inducers such as death inducing ligand TRAIL (TNFSF10) and pro-apoptotic Bax were also up-regulated. This comprehensive description of altered gene expression within IPF fibroblasts sheds further light on the complex interactions that characterize IPF. Further studies including therapeutic interventions directed at these pathways hold promise for the treatment of this devastating disease. 58 samples of total RNA isolated from 12 lungs of patients with end-stage idiopathic pulmonary fibrosis and 6 donors of normal lungs (controls) who were designated brain dead, non-diseased donors whose lungs failed criteria for transplantation and who were organ donors for research. RNA extraction followed the Qiagen RNeasy Kit using QIshredder columns for shredding of DNA contiminants. Experimental/control samples were amplified amino-allylated RNA labeled with Cy5 and Stratagene Reference RNA was amplified and amino-allylated and labeled with Cy3. Amplification was one round using Ambion MessageAmp II kit with amino-allylated UTP according to the protocol of the Duke University Institute for Genome Sciences and Policy. Amplification and amino-allylation of the Stratagene Reference RNA and Hybridization of Reference with patient samples and controls was done by the Duke Institute for Genomic Sciences and Policy.
2010-05-19 | E-GEOD-17978 | biostudies-arrayexpress
Project description:Archived lung tissues of patients with IPF were obtained from the tissue bank of the Department of Pathology at the University of Pittsburgh. The diagnosis of IPF was confirmed by open lung biopsy. All patients fulfilled the criteria of the American Thoracic Society and European Respiratory Society for the diagnosis of IPF. Normal histology lung tissues resected from patients with lung cancer were used as controls. Keywords: parallel sample
2005-08-08 | GSE2052 | GEO
Project description:There is microscopic spatial and temporal heterogeneity of pathologic changes in idiopathic pulmonary fibrosis (IPF) lung tissue, which may relate to heterogeneity in pathophysiological mediators of disease and clinical progression. We measured gene expression in samples from lung biopsies or explants in order to assess relationships with pathological features and systemic biomarkers.
2014-10-14 | GSE53845 | GEO
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.
2018-07-03 | GSE116525 | GEO
Project description:The activated fibroblast is the central effector cell for the progressive fibrotic process that characterizes idiopathic pulmonary fibrosis (IPF). An understanding of the genomic phenotype of this cell in isolation is essential to the understanding of disease pathogenesis and is integral to strategizing therapeutic trials. Employing a unique technique that minimizes cellular phenotypic alterations, we characterized the genomic phenotype of non-cultured pulmonary fibroblasts from the lungs of patients with advanced IPF. This approach revealed several novel genes and pathways previously unreported in IPF fibroblasts. Specifically, we demonstrate altered expression in proteasomal constituents, ubiquitination mediators, the Wnt pathway and several cell cycle regulators suggestive of loss of normal cell cycle controls. The pro-inflammatory cytokine CXCL12 was also up-regulated which may provide a mechanism for fibrocytes’ recruitment, while up-regulated oncogenic KIT may promote fibroblast over proliferation. Paradoxically, pro-apoptotic inducers such as death inducing ligand TRAIL (TNFSF10) and pro-apoptotic Bax were also up-regulated. This comprehensive description of altered gene expression within IPF fibroblasts sheds further light on the complex interactions that characterize IPF. Further studies including therapeutic interventions directed at these pathways hold promise for the treatment of this devastating disease.
2010-05-19 | GSE17978 | GEO
Project description:To investigate the comprehensive mRNA expression profile of ILC2s from IPF patients, we performed bulk RNA-sequencing analysis of ILC2s sorted from IPF patients and healthy controls.
2023-11-04 | GSE194244 | GEO