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GSE58233
Homo sapiens
8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide analysis in human colorectal cancer cells reveals ischemia-mediated expression of motility genes via DNA hypomethylation.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
DNA hypomethylation is an important epigenetic modification found to occur in many different cancer types, leading to the upregulation of previously silenced genes and loss of genomic stability. We previously demonstrated that hypoxia and hypoglycaemia (ischemia), two common micro-environmental changes in solid tumors, decrease DNA methylation through the downregulation of DNMTs in human colorectal cancer cells. Here, we utilized a genome-wide cross-platform approach to identify genes hypomethylated and upregulated by ischemia. Following exposure to hypoxia or hypoglycaemia, methylated DNA from human colorectal cancer cells (HCT116) was immunoprecipitated and analysed with an Affymetrix promoter array. Additionally, RNA was isolated and analysed in parallel with an Affymetrix expression array. Ingenuity pathway analysis software revealed that a significant proportion of the genes hypomethylated and upregulated were involved in cellular movement, including PLAUR and CYR61. A Matrigel invasion assay revealed that indeed HCT116 cells grown in hypoxic or hypoglycaemic conditions have increased mobility capabilities. Confirmation of upregulated expression of cellular movement genes was performed with qPCR. The correlation between ischemia and metastasis is well established in cancer progression, but the molecular mechanisms responsible for this common observation have not been clearly identified. Our novel results suggest that hypoxia and hypoglycaemia may be driving changes in DNA methylation through downregulation of DNMTs. This is the first report to our knowledge that provides an explanation for the increased metastatic potential seen in ischemic cells; i.e. that ischemia could be driving DNA hypomethylation and increasing expression of cellular movement genes.
Publication Title
Genome-wide analysis in human colorectal cancer cells reveals ischemia-mediated expression of motility genes via DNA hypomethylation.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The role of Tfr1 in non-erythroid tissues remains elusive due to the embryonic lethality of the Tfr1 global knockout mouse model. To bypass this problem, we generated a mouse model in which Tfr1 was conditionally deleted in intestinal epithelial cells (IECs). These mice developed severe IEC disruption, characterized by blunted villi, edema, loss of proliferative intervillus IECs, accumulation of lipids, and early neonatal lethality. Strikingly, a wide range of genes associated with epithelial-to-mesenchymal transition were highly upregulated in IEC lacking Tfr1. Additionally, candidate vesicular transport and sorting genes implicated in lipid absorption and trafficking were downregulated. Surprisingly, the presence of a mutant allele of Tfr1, which is unable to bind to iron-loaded transferrin, was capable of rescuing the lethality, intestinal epithelial homeostasis, and proliferation in a majority of the Tfr1 conditional knockout mice.
Publication Title
Noncanonical role of transferrin receptor 1 is essential for intestinal homeostasis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2000
Description
Ghrelin, an orexigenic gut-derived peptide, is gaining increasing attention due to its multifaceted role in a number of physiological functions, including metabolism, cardiovascular health, stress and reproduction. Ghrelin exists in circulation primarily as des-acylated and acylated ghrelin. Des-acyl ghrelin, until recently considered to be an inactive form ghrelin, is now known to have independent physiological functionality. However, the relative contribution of acyl and des-acyl ghrelin to reproductive development and function is currently unknown. Here we used ghrelin-O-acyltransferase (GOAT) knockout (KO) mice that have no measurable levels of endogenous acyl ghrelin and chronically high levels of des-acyl ghrelin, to characterise how the developmental and life-long absence of acyl ghrelin affects ovarian development and reproductive capacity. We have combined ovarian transcriptome analysis using RNA sequencing with measures of ovarian morphometry, as well as with the assessment of markers of reproductive maturity and the capacity to breed. Our data show pronounced specific changes in the ovarian transcriptome in the juvenile GOAT KO ovary, indicative of advanced ovarian development. These changes corresponded with diminished ovarian reserve in the juvenile and adult ovaries of these mice, due to a continuous reduction in the number of small follicle populations. These changes did not affect the timing of puberty onset or reproductive capacity under optimal conditions. These data suggest that an absence of acyl ghrelin does not prevent reproductive success but that appropriate levels of acyl and des-acyl ghrelin may be necessary for optimal ovarian maturation. Overall design: 4 WT and 4 GOAT KO ovaries were used for this analysis
Publication Title
Acylated Ghrelin Supports the Ovarian Transcriptome and Follicles in the Mouse: Implications for Fertility.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
We deleted Tfr1 in the heart to determine the role of Tfr1 in iron uptake in normal cardiac funciton We used microarrays to identify global gene changes associated with deletion of Tfr1 in skeletal muscle
Publication Title
Lethal Cardiomyopathy in Mice Lacking Transferrin Receptor in the Heart.
Sample Metadata Fields
Age, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Methylated DNA binding protein 2 (MBD2) has been shown to bind specific methylated promoters and suppress transcription. Here we systematically investigate MBD2 suppression by overexpressing MBD2 in MCF-10A cells and generating gene expression profiles of overexpressing cells and normal MCF-10A cells.
Publication Title
Methylated DNA binding domain protein 2 (MBD2) coordinately silences gene expression through activation of the microRNA hsa-mir-496 promoter in breast cancer cell line.
Sample Metadata Fields
Cell line, Treatment
View Samples- Rattus norvegicus
- 45 Downloadable Samples
- Affymetrix Rat Gene 1.1 ST Array (ragene11st)
Description
Introduction: Renal ischemia-reperfusion (IR) causes acute kidney injury (AKI) with high mortality and morbidity. The objective of this study was to ameliorate kidney IR injury and identify novel biomarkers for kidney injury and repair. Methods: Left renal ischemia was induced in rats by clamping renal artery for 45 minutes, followed by reperfusion and right nephrectomy. Thirty minutes prior to ischemia, rats (n=8/group) received Valproic Acid (150 mg/kg; VPA), Dexamethasone (3 mg/kg; Dex) or Vehicle (Saline) intraperitoneally. Animals were sacrificed at 3h, 24h or 120h post- IR and blood, urine and kidney were collected. Results: Serum creatinine (mg/dL) at 24 h IR in VPA (2.71.8) and Dex (2.31.2) was reduced (P<0.05) compared to Vehicle (3.80.5). At 3h post-IR, urine albumin (mg/ml) was higher in Vehicle (1.470.10), VPA (0.840.62) and Dex (1.040.73) compared to uninjured/untreated control (0.140.26) group. At 24h post-IR urine Lipocalin-2 (g/ml) was significantly higher (P<0.05) in VPA, Dex and Vehicle groups (9.61-11.36) compared to uninjured/untreated control (0.67o.29); also, Kidney Injury Molecule-1 (KIM-1; ng/ml) was significantly higher in VPA, Dex and Vehicle groups (13.7-18.7) compared uninjured/untreated control (1.71.9). KIM-1 levels were significantly (P<0.05) higher in all groups compared to uninjured/untreated control levels. Histopathology at 3h post IR demonstrated (P<0.05) reduction in ischemic injury in the renal cortex in VPA (Grade 1.6 1.5) compared to Vehicle (Grade 2.91.1) group. Inflammatory cytokines IL1 and IL6 were down-regulated in VPA and Dex groups. BCL2 was higher in VPA group. DNA microarray analysis demonstrated reduced stress response and injury, and improved recovery related gene expression in the kidneys of VPA treated animals. Conclusions: VPA administration reduced kidney IR injury and improved regeneration. KIM-1 and Lipocalin-2 appear to be promising early urine biomarkers of acute ischemic kidney injury.
Publication Title
Effects of valproic acid and dexamethasone administration on early bio-markers and gene expression profile in acute kidney ischemia-reperfusion injury in the rat.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Lesions of chronic idiopathic urticaria (CIU) showed significant up-regulation of 506 genes and reduced expression of 51 genes.
Publication Title
Gene expression profiles in chronic idiopathic (spontaneous) urticaria.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 221 Downloadable Samples
- Illumina HiSeq 2500
Description
Here we analyse single cell transcriptome profiles of EZH2-deficient human embroynic stem cells Overall design: Single cell transcriptome (mRNA-Seq) from Ezh2-/- (Null) and EZH2+/+ (WT) human ESC
Publication Title
Deletion of the Polycomb-Group Protein EZH2 Leads to Compromised Self-Renewal and Differentiation Defects in Human Embryonic Stem Cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Recent advances in multiple whole genome technologies provide unprecedented opportunities to profile epigenomic signatures in cancer cells. Previously we used a human gene promoter tiling microarray platform to identify genome-wide DNA methylation changes in a cell line model of breast cancer metastasis. Interestingly, the clustered nature of epigenetic targets that we identified, along with our concurrent karyotype analyses, have now led us to hypothesize that complex genomic alterations in cancer cells (deletions, translocations and ploidy) may be superimposed over promoter-specific methylation events that are responsible for gene-specific expression changes.
Publication Title
Multi-platform whole-genome microarray analyses refine the epigenetic signature of breast cancer metastasis with gene expression and copy number.
Sample Metadata Fields
Cell line
View Samples