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GSE18637
Homo sapiens
18 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human airway epithelial cells cultured in vitro at air-liquid interface (ALI) form a pseudostratified epithelium that forms tight junctions and cilia, and produces mucin, and are widely used as a model of differentiation, injury, and repair. To assess how closely the transcriptome of ALI epithelium matches that of in vivo airway epithelial cells, we used microarrays to compare the transcriptome of human large airway epithelial cells cultured at ALI with the transcriptome of large airway epithelium obtained via bronchoscopy and brushing. Gene expression profiling showed global gene expression correlated well between ALI cells and brushed cells, but there were some differences. Gene expression patterns mirrored differences in proportions of cell types (ALI have higher percentages of basal cells, brushed cells have higher percentages of ciliated cells), with ALI cells expressing higher levels of basal cell-related genes and brushed cells expressing higher levels of cilia-related genes. Pathway analysis showed ALI cells had increased expression of cell cycle and proliferation genes, while brushed cells had increased expression of cytoskeletal organization and humoral immune response genes. Overall, ALI cells are a good representation of the in vivo airway epithelial transcriptome, but for some biologic questions, the differences in the in vitro vs in vivo environments need to be considered.
Publication Title
Do airway epithelium air-liquid cultures represent the in vivo airway epithelium transcriptome?
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Medroxyprogesterone acetate (MPA) is a progestin that can bind to and activate progesterone, androgen and glucocorticoid receptors. However, it is not known which receptor mediates MPA action in a cellular context where all three of these receptors are co-expressed and functional.
Publication Title
Anti-proliferative transcriptional effects of medroxyprogesterone acetate in estrogen receptor positive breast cancer cells are predominantly mediated by the progesterone receptor.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 24 Downloadable Samples
Affymetrix Human Full Length HuGeneFL Array (hu6800), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Whereas cilia damage and reduced cilia beat frequency have been implicated as causative of reduced mucociliary clearance in smokers, theoretically mucociliary clearance could also be affected by cilia length. Based on models of mucociliary clearance predicting cilia length must exceed the 6 -7 m airway surface fluid depth to generate force in the mucus layer, we hypothesized cilia height may be decreased in airway epithelium of normal smokers compared to nonsmokers.
Publication Title
Smoking is associated with shortened airway cilia.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Full Length HuGeneFL Array (hu6800)
Description
Down-regulation of the Notch Differentiation Pathway in the Human Airway Epithelium in Normal Smokers and Smokers with Chronic Obstructive Lung Disease
Publication Title
Down-regulation of the notch pathway in human airway epithelium in association with smoking and chronic obstructive pulmonary disease.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 121 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To help define the genes associated with mucus synthesis and secretion in the human small airway epithelium, we hypothesized that comparison of the transcriptomes of the small airway epithelium of individuals that express high vs low levels of MUC5AC, a major secretory mucin and the major component of airway mucus, could be used as a probe to identify the genes related to human small airway mucus production / secretion. Genome-wide comparison between healthy nonsmokers grouped as high MUC5AC expressors vs low MUC5AC expressors identified significantly up-regulated and down-regulated genes in the high vs low expressors. Based on the literature, genes in the up-regulated list were used to identify a 73 MUC5AC-associated core gene list with 9 categories: mucus components; mucus-producing cell differentiation-related transcription factor; mucus-producing cell differentiation-related pathway or mediator; post-translational modification of mucin; vesicle transport; endoplasmic reticulum stress-related; secretory granule-associated; mucus secretion-related regulator and mucus hypersecretory-related ion channel. The identification of the genes associated with increased small airway mucin production in humans should be useful in identifying therapeutic targets to treat small airway mucus hypersecretion.
Publication Title
Genes associated with MUC5AC expression in small airway epithelium of human smokers and non-smokers.
Sample Metadata Fields
Specimen part, Race, Time
View Samples- Homo sapiens
- 121 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Healthy individuals exposed to low levels of cigarette smoke have a decrement in lung function and higher risk for lung disease compared to unexposed individuals. We hypothesized that healthy individuals exposed to low levels of tobacco smoke must have biologic changes in the small airway epithelium compared to healthy unexposed individuals. Methods: Small airway epithelium was obtained by bronchoscopy from 121 individuals; microarrays assessed genome wide gene expression, and urine nicotine and cotinine were used to categorized subjects as nonsmokers, active smokers, and low exposure. The gene expression data was used to determine the threshold and ID50 of urine nicotine and cotinine at which the small airway epithelium showed abnormal responses. Results: There was no threshold of urine nicotine without an abnormal small airway epithelial response, and only a slightly above detectable threshold abnormal response for cotinine. The nicotine ID50 for nicotine was 25 ng/ml and cotinine 104 ng/ml. Conclusions: The small airway epithelium detects and responds to low levels of tobacco smoke with transcriptome modifications. This provides biologic correlates of epidemiologic studies linking low level tobacco smoke exposure to lung health risk, health, identifies genes in the lung cells most sensitive to tobacco smoke and defines thresholds at the lung epithelium responds to inhaled tobacco smoke.
Publication Title
Threshold of biologic responses of the small airway epithelium to low levels of tobacco smoke.
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
- 4 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Genome-wide association studies have identified a locus within the second intron of the FGFR2 gene that is consistently the most strongly associated with estrogen receptor-poisive breast cancer risk. However, we know little about the mechanisms by which the FGFR2 locus mediates risk or the pathways in which multiple risk loci may combine to cause disease. Previously, a systems biology approach was adopted to elucidate the regulatory networks operating in MCF-7 breast cancer cells in order to examine the role of FGFR2 in mediating risk. Here, the same approach has been employed using a number of different estrogen receptor-positive breast cancer cell lines in order to see if the previous findings are reproducible and consistent in estrogen receptor-positive disease.
Publication Title
Regulators of genetic risk of breast cancer identified by integrative network analysis.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Identifying the effect of the co-chaperone SGTA on global androgen receptor transcriptional activity in C4-2B prostate cancer cells with view to further elucidating the broader biological role of SGTA on other signaling pathways within prostate cancer cells
Publication Title
Knockdown of the cochaperone SGTA results in the suppression of androgen and PI3K/Akt signaling and inhibition of prostate cancer cell proliferation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Background. Nuclear factor I-A (NFI-A), a phylogenetically conserved transcription/replication protein, plays a crucial role in mouse brain development. Previous studies showed that disruption of the Nfia gene in mice leads to perinatal lethality, corpus callosum agenesis, and hydrocephalus.
Publication Title
Gene expression analysis of nuclear factor I-A deficient mice indicates delayed brain maturation.
Sample Metadata Fields
No sample metadata fields
View Samples