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GSE43079
Homo sapiens
34 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The small airway epithelium (SAE), the first site of smoking-induced lung pathology, exhibits genome-wide changes in gene expression in response to cigarette smoking. Based on the increasing evidence that the epigenome can respond to external stimuli in a rapid manner, we assessed the SAE of smokers for genome-wide DNA methylation changes compared to nonsmokers, and whether changes in SAE DNA methylation were linked to the transcriptional output of these cells. Using genome-wide methylation analysis of SAE DNA of nonsmokers and smokers, the data identified 204 unique genes differentially methylated in SAE DNA of smokers compared to nonsmokers, with 67% of the regions with differential methylation occurring within 2 kb of the transcriptional start site. Among the genes with differential methylation were those related to metabolism, transcription, signal transduction and transport. For the differentially methylated genes, 34 exhibited a correlation with gene expression, 53% with an inverse correlation of DNA methylation with gene expression and 47% a direct correlation. These observations provide evidence that cigarette smoking alters the DNA methylation patterning of the SAE and that, for some genes, these changes are associated with the smoking-related changes in gene expression.
Publication Title
Cigarette smoking induces small airway epithelial epigenetic changes with corresponding modulation of gene expression.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Waterpipe smoking induces epigenetic changes in the small airway epithelium.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Waterpipe (also called hookah, shisha, or narghile) smoking is a common form of tobacco use in the Middle East. Its use is becoming more prevalent in Western societies, especially among young adults as an alternative form of tobacco use to traditional cigarettes. While the risk to cigarette smoking is well documented, the risk to waterpipe smoking is not well defined with limited information on its health impact at the epidemiologic, clinical and biologic levels with respect to lung disease. Based on the knowledge that airway epithelial cell DNA methylation is modified in response to cigarette smoke and in cigarette smoking-related lung diseases, we assessed the impact of light-use water-pipe smoking on DNA methylation of the small airway epithelium (SAE) and whether changes in methylation were linked to the transcriptional output of the cells. Small airway epithelium was obtained from 7 nonsmokers and 7 light-use (2.6 1.7 sessions/wk) waterpipe-only smokers. Genome-wide comparison of SAE DNA methylation of waterpipe smokers to nonsmokers identified 727 probesets differentially methylated (fold-change >1.5, p<0.05) representing 673 unique genes. Dominant pathways associated with these epigenetic changes include those linked to G-protein coupled receptor signaling, aryl hydrocarbon receptor signaling and xenobiotic metabolism signaling, all of which have been associated with cigarette smoking and lung disease. Of the genes differentially methylated, 11.3% exhibited a corresponding significant (p<0.05) change in gene expression with enrichment in pathways related to regulation of mRNA translation and protein synthesis (eIF2 signaling and regulation of eIF4 and p70S6K signaling). Overall, these data demonstrate that light-use waterpipe smoking is associated with epigenetic changes and related transcriptional modifications in the SAE, the cell population demonstrating the earliest pathologic abnormalities associated with chronic cigarette smoking.
Publication Title
Waterpipe smoking induces epigenetic changes in the small airway epithelium.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 2 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
We report global RNA expression profiles from whole zebrafish hearts 24 hours after ventricle amputation. Zebrafish were exposed to atropine or water following surgery.
Publication Title
Nerves Regulate Cardiomyocyte Proliferation and Heart Regeneration.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Directing differentiation of human embryonic stem cells (hESC) into specific cell types using an easy and reproducible protocol is a perquisite for the clinical use of hESC in regenerative medicine protocols. Here, we report the generation of mesodermal cells with differentiation potential to myocytes, osteoblasts, chondrocytes and adipocytes. We demonstrate that during hESC differentiation as embryoid bodies (EB), inhibition of TGF-b/Activin/Nodal signaling using SB-431542 (SB) markedly up-regulated paraxial mesodermal markers (TBX6, TBX5), early myogenic transcriptional factors (Myf5, Pax7) as well as myocyte committed markers (NCAM, CD34, Desmin, MHC (fast), alpha-smooth muscle actin, Nkx2.5, cTNT). Establishing EB outgrowth cultures (SB-OG) in the presence of SB (1 uM) led to further enrichment of cells expressing markers for myocyte progenitor cell: CD34+ (33%), NCAM+ (CD56) (73%), PAX7 (25%) and mature myocyte proteins (MYOD1, tropomyocin, fast MHC an
Publication Title
Enhanced differentiation of human embryonic stem cells to mesenchymal progenitors by inhibition of TGF-beta/activin/nodal signaling using SB-431542.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Autoantibodies that arise in autoimmunity can be present years to decades prior to the onset of disease manifestations. This suggests that the initial autoimmune trigger involves a peripheral lymphoid component, which then drives disease pathology in local tissues later in life. To explore the impact of early peripheral immune dysregulation on the progression of Sjgrens Syndrome, we blocked the CD40-CD40L pathway in young female NOD.H-2h4 mice at 4 weeks of age with a single injection of anti-CD40L antibody, and collected total salivary gland at the age of week 8, 16 and 24. RNA was extracted and submitted to transcriptome profiling using Affymetrix microarray.
Publication Title
Autoimmune manifestations in aged mice arise from early-life immune dysregulation.
Sample Metadata Fields
Treatment
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome U34 Array (rgu34a)
Description
We measured gene expression in the adrenal glands of the Spontaneously Hypertensive Rat (SHR) and Wistar-Kyoto rat (WKY) using Affymetrix RG-U34A GeneChips. All rats were aged-matched at 4-weeks. The rats were obtained from the colonies at the Univeristy of California San Diego, La Jolla, CA.
Publication Title
Common genetic mechanisms of blood pressure elevation in two independent rodent models of human essential hypertension.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
We performed Affymetrix MG-U74Av2 GeneChip experiements on mRNA from the adrenal glands of the BPH hypertensive and BPL hypotensive mouse strains. All mice were aged-matched at 5 weeks. We obtained the mice from Jackson Laboratories, Bar Harbor, ME.
Publication Title
Neuroendocrine transcriptome in genetic hypertension: multiple changes in diverse adrenal physiological systems.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Cancer cells interact with surrounding stromal fibroblasts during tumorigenesis, but the complex molecular rules that govern these interactions remain poorly understood, thus hindering the development of therapeutic strategies to target cancer stroma. We have taken a mathematical approach to begin defining these rules by performing large-scale quantitative analysis of fibroblast effects on cancer cell proliferation across more than four hundred heterotypic cell line pairings. Systems-level modeling of this complex dataset using singular value decomposition revealed that normal tissue fibroblasts variably express at least two functionally distinct activities, one which reflects transcriptional programs associated with activated mesenchyme, that act either coordinately or at cross-purposes to modulate cancer cell proliferation. To gain insight into the molecular identity of these fibroblast activities, we isolated RNA from 36 human skin and lung fibroblast cell line monocultures from Coriell Repositories or ATCC and performed microarray-based gene expression profiling using Affymetrix gene chips.
Publication Title
Systems-level modeling of cancer-fibroblast interaction.
Sample Metadata Fields
Sex, Age, Race
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
DLK1/FA-1 (delta-like 1/fetal antigen-1) is a transmembrane protein belonging to Notch/Delta family that acts as a membrane-associated or a soluble protein to regulate regeneration of a number of adult tissues. Here, we examined the role of DLK1/FA-1 in bone biology using osteoblast-specific-Dlk1 over-expressing mice (Col1-Dlk1). Col1-Dlk1 mice displayed growth retardation and significantly reduced total body weight and bone mineral density (BMD). CT-scanning revealed a reduced trabecular and cortical bone volume fraction. Tissue-level histomorphometric analysis demonstrated decreased bone formation rate and enhanced bone resorption in Col1-Dlk1 as compared to WT. At a cellular level, DLK1 markedly reduced the total number of bone marrow (BM)-derived CFU-F, as well as their osteogenic capacity. In a number of in vitro culture systems, DLK1 stimulated osteoclastogenesis indirectly through osteoblast-dependent increased production of pro-inflammatory bone resorbing cytokines (e.g, Il7, Tnfa and Ccl3). We found that ovariectomy (ovx)-induced bone loss was associated with increased production of DLK1 in bone marrow by activated T-cells. However, Dlk1-/- mice were protected from ovx-induced bone loss. Thus, we identified DLK1 as a novel regulator of bone mass that function to inhibit bone formation and to stimulate bone resorption. Increasing DLK1 production by T-cells under estrogen deficiency suggests its possible use as a therapeutic target for preventing postmenopausal bone loss.
Publication Title
DLK1 is a novel regulator of bone mass that mediates estrogen deficiency-induced bone loss in mice.
Sample Metadata Fields
Specimen part
View Samples