Filters
Technology
Platform
GSE63127
Homo sapiens
202 Downloadable Samples
Affymetrix Human Full Length HuGeneFL Array (hu6800), Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Smoking-induced lung disease is one of the most prevalent forms of lung disease but also one of the more diverse. Based on the phenotypic diversity caused by the same environmental stress, we hypothesized that smoking may induce changes in lung cell expression of genes that, with specific variants, are causative of monogenic lung disease, i.e., not that smoking induces a phenocopy of a genetic disease, but smoking may subtly modify the expression of genes known to be associated with genetic disorders with distinct lung disease phenotypes. To assess this hypothesis, and based on the knowledge that most smoking-related disease phenotypes start in the small airway epithelium, we asked: are the genes associated with the monogenic lung disorders expressed in the small airway epithelium, and if so, does smoking alter the expression of these genes? To accomplish this, we examined small airway epithelium expression of 92 genes known to be associated with 17 monogenic lung disorders in 230 samples of small airway epithelium (SAE) obtained from healthy nonsmokers and healthy smokers without any clinical evidence of disease. Of the 86 monogenic disorder-related genes we found expressed in the SAE, strikingly, 37 were significantly differentially expressed in normal smokers compared to normal nonsmokers (p<0.05, Benjamini-Hochberg correction for multiple comparisons). The data demonstrates that the effect of smoking on the transcriptome of small airway epithelium includes significantly altered regulation of the genes responsible for known monogenic disorders.
Publication Title
Cigarette Smoking Induces Changes in Airway Epithelial Expression of Genes Associated with Monogenic Lung Disorders.
Sample Metadata Fields
Sex, Age, Race
View Samples- Homo sapiens
- 52 Downloadable Samples
Illumina HiSeq 2000
Description
Rationale: Genome-wide association studies (GWAS) and candidate gene studies have identified a number of loci linked to susceptibility of chronic obstructive pulmonary disease (COPD), a smoking-related disorder that originates in the airway epithelium. Objectives: Since airway basal cell (BC) stem/progenitor cells exhibit the earliest abnormalities associated with smoking (hyperplasia, squamous metaplasia), we hypothesized that smoker BC have a dysregulated transcriptome linked, in part, to known GWAS/candidate gene loci. Methods: Massive parallel RNA sequencing was used to compare the transcriptome of BC purified from the airway epithelium of healthy nonsmokers (n=10) and smokers (n=7). The chromosomal location of the differentially expressed genes was compared to loci identified by GWAS and candidate gene studies to confer risk for COPD. Measurements and Main Results: Smoker BC have 676 known genes differentially expressed compared to nonsmoker BC, dominated by smoking up-regulation. Strikingly, 166 (25%) of these genes are located on chromosome 19, with 13 localized to 19q13.2 (p<10-4 compared to chance), including TGFB1, LTBP4, EGLN2 and NFKBIB, genes associated with risk for COPD. Conclusions: These observations provide the first direct link of known genetic risks for smoking-related lung disease with the specific population of lung cells that undergoes the earliest changes associated with smoking. Overall design: The human airway basal cell transcriptome of 7 smokers versus 10 nonsmokers was compared using massive parallel RNA sequencing (Illumina HiSeq 2000).
Publication Title
Smoking dysregulates the human airway basal cell transcriptome at COPD risk locus 19q13.2.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 160 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes.
Sample Metadata Fields
Specimen part, Cell line, Race, Time
View Samples- Homo sapiens
- 160 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In the process of seeking novel lung host defense regulators by analyzing genome-wide RNA sequence data from normal human airway epithelium, we detected expression of POU2AF1, a known transcription co-factor previously thought to be expressed only in lymphocytes. Lymphocyte contamination of human airway epithelial samples obtained by bronchoscopy and brushing was excluded by immunohistochemistry staining, the observation of up-regulation of POU2AF1 in purified airway basal stem/progenitor cells undergoing differentiation and analysis of differentiating single basal cell clones. Lentivirus-mediated up-regulation of POU2AF1 in airway basal cells induced up-regulation of host defense genes, including MX1, IFIT3, IFITM and known POU2AF1 downstream genes HLA-DRA, ID2, ID3, IL6, BCL6. Interestingly, expression of these genes paralleled changes of POU2AF1 expression during airway epithelium differentiation in vitro, suggesting POU2AF1 helps to maintain a "host defense tone" even in pathogen-free condition. Cigarette smoke, a known risk factor for airway infection, suppressed POU2AF1 expression both in vivo in humans and in vitro in human airway epithelial cultures, accompanied by deregulation of POU2AF1 downstream genes. Finally, enhancing POU2AF1 expression in human airway epithelium attenuated the suppression of host defense genes by smoking. Together, these findings suggest a novel function of POU2AF1 as a potential regulator of host defense genes in the human airway epithelium.
Publication Title
POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes.
Sample Metadata Fields
Specimen part, Race, Time
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Unlike ovarian cancer, normal ovarian epithelium response to TGFb1 induced growth inhibition. This time course study tried to idenify genes that showed changes after additionof TGFb1 in immortalized ovarian surface epithelial cells (IOSE) which is derived from normal ovarian epithelial cells
Publication Title
An integrative ChIP-chip and gene expression profiling to model SMAD regulatory modules.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
A variety of cell cultures models and in vivo approaches have been used to study gene expression during chondrocyte differentiation. The extent to which the in vitro models reflect bona fide gene regulation in the growth plate has not been quantified. In addition, studies that evaluate global gene expression changes among different growth plate zones are limited. To address these issues, we completed a microarray screen of three growth plate zones derived from manually segmented embryonic mouse tibiae. Classification of genes differentially expressed between each respective growth plate zone, functional categorization as well as characterization of gene expression patterns, cytogenetic loci, signaling pathways and functional motifs confirmed documented data and pointed to novel aspects of chondrocyte differentiation. Parallel comparisons of the microdissected tibiae data set to our previously completed micromass culture screen further corroborated the suitability of micromass cultures for modeling gene expression in chondrocyte development. The micromass culture system demonstrated striking similarities to the in vivo microdissected tibiae screen; however, the micromass system was unable to accurately distinguish gene expression differences in the hypertrophic and mineralized zones of the growth plate. These studies will allow us to better understand zone-specific gene expression patterns in the growth plate. Ultimately, this work will help define both the genomic context in which genes are expressed in the long bones and the extent to which the micromass culture system is able to recapitulate chondrocyte development in endochondral ossification.
Publication Title
Genome-wide analyses of gene expression during mouse endochondral ossification.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- IlluminaHiSeq2000
Description
Genes encoding subunits of SWI/SNF chromatin remodeling complexes are collectively mutated in ~20% of all human cancers. Although ARID1A is the most frequent target of mutations, the mechanism by which its inactivation promotes tumorigenesis is unclear. Here, we demonstrate that Arid1a functions as a tumor suppressor in the mouse colon, but not the small intestine, and that invasive ARID1A-deficient adenocarcinomas resemble human colorectal cancer (CRC). These tumors lack deregulation of APC/beta-catenin, crucial gatekeepers in common forms of intestinal cancer. ARID1A normally targets SWI/SNF complexes to enhancers, where they function in coordination with transcription factors (TFs) to facilitate gene activation. ARID1B preserves SWI/SNF function in ARID1A-deficient cells, but defects in SWI/SNF targeting and control of enhancer activity cause extensive dysregulation of gene expression. These findings represent an advance in colon cancer modeling and implicate enhancer-mediated gene regulation as a principal tumor suppressor function of ARID1A. Overall design: RNA-seq in HCT116 colorectal cancer line for ARID1A WT, and Homozygous and Heterozygous KO cells.
Publication Title
ARID1A loss impairs enhancer-mediated gene regulation and drives colon cancer in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
Genes encoding subunits of SWI/SNF chromatin remodeling complexes are collectively mutated in ~20% of all human cancers. Although ARID1A is the most frequent target of mutations, the mechanism by which its inactivation promotes tumorigenesis is unclear. Here, we demonstrate that Arid1a functions as a tumor suppressor in the mouse colon, but not the small intestine, and that invasive ARID1A-deficient adenocarcinomas resemble human colorectal cancer (CRC). These tumors lack deregulation of APC/beta-catenin, crucial gatekeepers in common forms of intestinal cancer. ARID1A normally targets SWI/SNF complexes to enhancers, where they function in coordination with transcription factors (TFs) to facilitate gene activation. ARID1B preserves SWI/SNF function in ARID1A-deficient cells, but defects in SWI/SNF targeting and control of enhancer activity cause extensive dysregulation of gene expression. These findings represent an advance in colon cancer modeling and implicate enhancer-mediated gene regulation as a principal tumor suppressor function of ARID1A. Overall design: RNA-seq in Primary Colon Epithelial cells form WT and ARID1A-KO mice.
Publication Title
ARID1A loss impairs enhancer-mediated gene regulation and drives colon cancer in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The relevance of DNA-dependent poly-ADP ribose production for neuronal differentiation of adult stem- and progenitor cells from the SVZ was studied. To identify genes whose up- or downregulation during neuronal differentiation requires the activity of poly-ADP-Ribosylase (PARP) 1 or 2, SVZ-derived adult neurosphere cultures were differentiated in the presence or absence of Olaparib.
Publication Title
MEIS homeodomain proteins facilitate PARP1/ARTD1-mediated eviction of histone H1.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 14 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
A key event in the pathogenic process of prion diseases is the conversion of the cellular prion protein (PrPC) to an abnormal and protease-resistant isoform (PrPSc). Mice lacking PrP are resistant to prion infection, and down-regulation of PrPC during prion infection prevents neuronal loss and the progression to clinical disease. These results are suggestive of the potential beneficial effect of silencing PrPC during prion diseases. However, the silencing of a protein that is widely expressed throughout the CNS could be detrimental to brain homeostasis. The physiological role of PrPC remains still unclear, but several putative functions have been proposed. Among these, several lines of evidence support PrPC function in neuronal development and maintenance.
Publication Title
Developmental influence of the cellular prion protein on the gene expression profile in mouse hippocampus.
Sample Metadata Fields
Specimen part
View Samples