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GSE11906
Homo sapiens
165 Downloadable Samples
Affymetrix Human Full Length HuGeneFL Array (hu6800), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Microarray technology provides a powerful tool for defining gene expression profiles of airway epithelium that lend insight into the pathogenesis of human airway disorders. The focus of this study was to establish rigorous quality control parameters to ensure that microarray assessment of the airway epithelium is not confounded by experimental artifact. Samples (total n=223) of trachea, large and small airway epithelium were collected by fiberoptic bronchoscopy of 144 individuals (42 healthy non-smokers, 49 healthy smokers, 11 symptomatic smokers, 22 smokers with lone emphysema with normal spirometry, and 20 smokers with COPD) were processed and hybridized to Affymetrix HG-U133 2.0 Plus microarrays. The pre- and post-chip quality control (QC) criteria established, included: (1) RNA quality, assessed by RNA Integrity Number (RIN) 7.0 using Agilent 2100 Bioanalyzer software; (2) cRNA transcript integrity, assessed by signal intensity ratio of GAPDH 3' to 5' probe sets 3.0; and (3) the multi-chip normalization scaling factor 10.0
Publication Title
Quality control in microarray assessment of gene expression in human airway epithelium.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 118 Downloadable Samples
- Affymetrix Human Full Length HuGeneFL Array (hu6800), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The apical junctional complex (AJC), composed of tight junctions and adherens junctions, is essential for maintaining epithelial barrier function. Since cigarette smoking and chronic obstructive pulmonary disease (COPD), the major smoking-induced disease, are both associated with increased lung epithelial permeability, we hypothesized that smoking alters the transcriptional program regulating AJC integrity in the small airway epithelium (SAE), the primary site of pathological changes in COPD. Transcriptome analysis revealed a global down-regulation of physiological AJC gene expression in the SAE of healthy smokers (n=53) compared to healthy nonsmokers (n=59), an observation associated with changes in molecular pathways regulating epithelial differentiation such as PTEN signaling and accompanied by induction of cancer-related AJC genes. Genome-wide co-expression analysis identified a smoking-sensitive AJC transcriptional network. The overall expression of AJC-associated genes was further decreased in COPD smokers (n=23). Exposure of human airway epithelial cells to cigarette smoke extract in vitro resulted in down-regulation of several AJC-related genes, accompanied by decreased transepithelial resistance. Thus, cigarette smoking alters the AJC gene expression architecture in the human airway epithelium, providing a molecular basis for the dysregulation of airway epithelial barrier function during the development of smoking-induced lung disease.
Publication Title
Cigarette smoking reprograms apical junctional complex molecular architecture in the human airway epithelium in vivo.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 85 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The initial site of smoking-induced lung disease is the small airway epithelium, which is difficult and time consuming to sample by fiberoptic bronchoscopy. We developed a rapid, office-based procedure to obtain trachea epithelium without conscious sedation from healthy nonsmokers (n=26) and healthy smokers (n=19, 27 15 pack-yr). Gene expression differences [fold-change >1.5, p< 0.01, Benjamini-Hochberg correction] were assessed with Affymetrix microarrays. 1,057 probe sets were differentially expressed in healthy smokers vs nonsmokers, representing >500 genes. Trachea gene expression was compared to an independent group of small airway epithelial samples (n=23 healthy nonsmokers, n=19 healthy smokers, 25 12 pack-yr). The trachea epithelium is more sensitive to smoking, responding with 3-fold more differentially-expressed genes than small airway epithelium. The trachea transcriptome paralleled the small airway epithelium, with 156 of 167 (93%) genes that are significantly up- and down-regulated by smoking in the small airway epithelium showing similar direction and magnitude of response to smoking in the trachea. Trachea epithelium can be obtained without conscious sedation, representing a less invasive surrogate canary for smoking-induced changes in the small airway epithelium. This should prove useful in epidemiologic studies correlating gene expression with clinical outcome in assessing smoking-induced lung disease.
Publication Title
Trachea epithelium as a "canary" for cigarette smoking-induced biologic phenotype of the small airway epithelium.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 6 Downloadable Samples
IlluminaHiSeq2000
Description
Our data demonstrated that Bcl6 directly binds and represses trafficking receptors S1pr1 and Grp183 by recruiting Hdac2 through the RD2 domain. Deregulation of these genes impairs B-cell migration and may contribute to the Germinal Center failure in Bcl6RD2MUT mice. Overall design: RNAseq was performed in endogenous BCL6-depleted OCI-LY1 cells rescued with either WT or RD mutant BCL6 (N=3 for each group).
Publication Title
The BCL6 RD2 domain governs commitment of activated B cells to form germinal centers.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 49 Downloadable Samples
- Illumina HiSeq 2000
Description
The EZH2 histone methyltransferase is required for B cells to form germinal centers (GCs). Here we show that EZH2 mediates GC formation through repression of cyclin-dependent kinase inhibitor CDKN1A (p21Cip1). Deletion of Cdkn1a rescued the GC reaction in Ezh2 knockout mice. To study the effects of EZH2 in primary GC B cells we generated and validated a 3D B cell follicular organoid system that mimics the endogenous GC reaction. Using this system we found that depletion of EZH2 suppressed G1 to S phase transition of GC B cells in a Cdkn1a dependent manner. GC B cells of Cdkn1a;Ezh2 double knockout mice exhibited high levels of phospho Rb, indicating that loss of Cdkn1a allows progression of cell cycle. Moreover, we show that the transcription factor E2F1 plays a major role in inducing EZH2 upregulation during the GC reaction. E2F1 deficient mice manifest impaired GC responses, which was rescued by restoring EZH2 expression, thus defining a positive feedback loop whereby EZH2 controls GC B cell proliferation by suppressing CDKN1A, allowing cell cycle progression with a concomitant phosphorylation of Rb and release of E2F1. Overall design: gene expression profiles of murine B cells
Publication Title
EZH2 enables germinal centre formation through epigenetic silencing of CDKN1A and an Rb-E2F1 feedback loop.
Sample Metadata Fields
Specimen part, Disease, Cell line, Subject, Time
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HiSeq 2000
Description
BCL6 inhibitor induces derepression of BCL6 target genes and shows a similar transcriptional program to BCL6 siRNA Overall design: Genome-wide profiling of mRNA transcript levels in human DLBCL cell line with BCL6 inhibitor and DMSO control.
Publication Title
Rationally designed BCL6 inhibitors target activated B cell diffuse large B cell lymphoma.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- Illumina HiSeq 2000
Description
Rationale: The BCL6 oncogene is constitutively activated by chromosomal translocations and amplification in ABC-DLBCLs, a class of DLBCLs that respond poorly to current therapies. Yet the role of BCL6 in maintaining these lymphomas has not been investigated. BCL6 mediates its effects by recruiting corepressors to an extended groove motif. Development of effective BCL6 inhibitors requires compounds exceeding the binding affinity of these corepressors. Objectives: To design small molecule inhibitors with superior potency vs. endogenous BCL6 ligands for unmet putative therapeutic needs such as targeting ABC-DLBCL. Findings: We used an in silico drug design functional-group mapping approach called SILCS to create a specific BCL6 inhibitor with 10-fold greater potency than endogenous corepressors. The compound, called FX1, binds in such a way as to occupy an essential region of the BCL6 lateral groove. FX1 disrupts BCL6 repression complex formation, reactivates BCL6 target genes, and mimics the phenotype of mice engineered to express BCL6 with lateral groove mutations. This compound eradicated established DLBCLs xenografts at low doses. Most strikingly, FX1 suppressed ABC-DLBCL cells as well as primary human ABC-DLBCL specimens ex vivo. Conclusions: ABC-DLBCL is a BCL6 dependent disease that can be targeted by novel inhibitors able to exceed the binding affinity of natural BCL6 ligands. Overall design: gene expression profiles of DLBCL cases
Publication Title
Rationally designed BCL6 inhibitors target activated B cell diffuse large B cell lymphoma.
Sample Metadata Fields
Specimen part, Subject
View Samples- Arabidopsis thaliana
- 6 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Transcript profiling and gene expression studies in NAE-treated seedlings: Seeds were germinated and seedlings maintained for 4 d in liquid MS media supplemented with 35 uM NAE(12:0)(N-lauroylethanolamine) prior to RNA isolation.
Publication Title
N-Acylethanolamine metabolism interacts with abscisic acid signaling in Arabidopsis thaliana seedlings.
Sample Metadata Fields
Age, Specimen part, Compound
View Samples- Homo sapiens
- 505 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We previously derived and validated a bronchial epithelial gene expression biomarker to detect lung cancer in current and former smokers. Given that bronchial and nasal epithelium gene expression is similarly altered by cigarette smoke exposure, we sought to determine if cancer-associated gene expression might also be detectable in more readily accessible nasal epithelium. Nasal epithelial brushings were prospectively collected from current and former smokers with pulmonary lesions suspicious for lung cancer in the AEGIS-1 (n=375) and AEGIS-2 (n=130) clinical trials and gene expression profiled using microarrays. Using the 375 AEGIS 1 samples, we identified 535 genes that were differentially expressed in the nasal epithelium of patients who were ultimately diagnosed with lung cancer vs. those with benign disease after one year of follow-up (p<0.001). Using bronchial gene expression data from 299 AEGIS-1 patients (including 157 patients with matched nasal and bronchial expression data), we found significantly concordant cancer-associated gene expression differences between the two airway sites (p<0.001). Differentially expressed genes were enriched for genes associated with the regulation of apoptosis, mitotic cell cycle, and immune system signaling. A nasal lung cancer classifier derived in the AEGIS-1 cohort that combined clinical factors and nasal gene expression had significantly higher AUC (0.80) and sensitivity (0.94) over a clinical-factor only model (p<0.05) in independent samples from the AEGIS-2 cohort (n=130). These results suggest that the airway epithelial field of lung cancer-associated injury in current and former smokers extends to the nose and demonstrates the potential of using nasal gene expression as a non-invasive biomarker for the detection of lung cancer.
Publication Title
Shared Gene Expression Alterations in Nasal and Bronchial Epithelium for Lung Cancer Detection.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HumanRef-8 v3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Plasmacytoid dendritic cells and C1q differentially regulate inflammatory gene induction by lupus immune complexes.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples