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Mus musculus
4 Downloadable Samples
Description
The ability of chromatin to switch back and forth from open euchromatin to closed heterochromatin is vital for transcriptional regulation and genomic stability, and subject to disruption by exposure to environmental agents such as hexavalent chromium. Cr(VI) exposure can cause chromosomal disruption through formation of Cr-DNA adducts, free radical-induced DNA damage, and DNA-Cr-protein and DNA-Cr-DNA cross-links, all of which may disrupt chromatin remodeling mechanisms responsible for maintenance or controlled modification of epigenetic homeostasis. In addition, dose-response analyses have shown that acute exposures to high-concentrations of Cr(VI) and chronic exposures to low-concentrations of the same agent lead to significantly different transcriptomic and genomic stability outcomes. To investigate how transcriptional responses to chromium exposure might correlate to structural changes in chromatin, we have used whole genome Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE) analysis coupled with deep sequencing to identify regions of the genome that switch from open to closed chromatin or vice versa in response to exposure to varying Cr(VI) concentrations. We find that the switch affects gene expression levels in the target areas that vary depending on Cr(VI) concentration. At either Cr(VI) concentration, chromatin domains surrounding binding sites for AP-1 transcription factors become significantly open, treatment whereas BACH2 and CTCF binding sites are open solely at the low and high concentrations, respectively. Our results suggest that FAIRE may be a useful technique to map chromatin elements targeted by DNA damaging agents for which there is no prior knowledge of their specificity, and to identify subsequent transcriptomic changes induced by those agents. Overall design: Cr25 treatment and control samples are in duplicate for RNA-seq, and no replicate for FAIRE-seq. Cr0.5 treatment and control samples are in duplicate for RNA-seq, and no replicate for FAIRE-seq.
Publication Title
Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE) analysis uncovers broad changes in chromatin structure resulting from hexavalent chromium exposure.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 53 Downloadable Samples
- Illumina HiSeq 2500
Description
The meningeal space is occupied by a diverse repertoire of innate and adaptive immune cells. CNS injury elicits a rapid immune response that affects neuronal survival and recovery, but the role of meningeal inflammation in CNS injury remains poorly understood. Here we describe group 2 innate lymphoid cells (ILC2s) as a novel cell type resident in the healthy meninges that is activated following CNS injury. ILC2s are present throughout the naïve mouse meninges, though are concentrated around the dural sinuses, and have a unique transcriptional profile relative to lung ILC2s. After spinal cord injury, meningeal ILC2s are activated in an IL-33 dependent manner, producing type 2 cytokines. Using RNAseq, we characterized the gene programs that underlie the ILC2 activation state. Finally, addition of wild type lung-derived ILC2s into the meningeal space of IL-33R-/- animals improves recovery following spinal cord injury. These data characterize ILC2s as a novel meningeal cell type that responds to and functionally affects outcome after spinal cord injury, and could lead to new therapeutic insights for CNS injury or other neuroinflammatory conditions. Overall design: ILC2s were isolated from 10 week C57/Bl6 mice with and without spinal cord injury (1 day post injury). 5 mice were pooled per group, with meninges dissected, digested, and FACs sorted (CD45+/DAPI-/Lin–/St2+/Thy1+) directly into RNA lysis buffer.
Publication Title
Characterization of meningeal type 2 innate lymphocytes and their response to CNS injury.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 29 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Background: Genes upregulated by low oxygen have been suggested as endogenous markers for tumor hypoxia. Yet, most of the genes investigated have shown inconsistent results, which have led to concerns about their ability to be true hypoxia markers. Previous studies have demonstrated that expression of hypoxia induced genes can be affected by extracellular pH (pH e ). Methods: Five different human cell lines (SiHa, FaDu DD, UTSCC5, UTSCC14 and UTSCC15) were exposed to different oxygen concentrations and pH (7.5 or 6.3), and gene expression analyzed with microarray (Affymetrix - Human Genome U133 Plus 2.0 Array). Results: An analysis of two of the cell lines using SAM identified 461 probesets that were able to separate the four groups Normal oxygen, normal pH , Low oxygen, normal pH , Normal oxygen, low pH and Low oxygen, low pH . From here it was possible to identify a fraction of probesets induced at low oxygen independent of pH in these two cell lines, this fraction included HIG2, NDRG1, PAI1 and RORA. Further verifi cation by qPCR highlighted the necessity of using more cell lines to obtain a robust gene expression profi les. To specifi cally select pH independent hypoxia regulated genes across more cell lines, data for FaDu DD, UTSCC5, UTSCC14 and UTSCC15 were analyzed to identify genes that were induced by hypoxia in each cell line, where the induction was not affected by low pH, and where the gene was not signifi cantly induced by low pH alone. Each cell line had 65 122 probesets meeting these criteria. For genes to be considered as target genes (hypoxia inducible pH independent), genes had to be present in three of four cell lines. Conclusion: The result is a robust hypoxia profile unaffected by pH across cell lines consisting of 27 genes. This study demonstrates a way to identify hypoxia markers by microarray, where other factors in the tumor microenvironment are taken into account.
Publication Title
Identifying pH independent hypoxia induced genes in human squamous cell carcinomas in vitro.
Sample Metadata Fields
Cell line
View Samples- Rattus norvegicus
- 15 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Background: Survival and function of insulin-secreting pancreatic -cells are markedly altered by changes in nutrient availability. In vitro, culture in 10 rather than 2mM glucose improves rodent -cell survival and function whereas glucose concentrations above 10mM are deleterious. Aim-Method: To identify the mechanisms of such -cell plasticity, we tested the effects of a 18h culture at 2, 5, 10 and 30mM glucose on the transcriptome of rat islets precultured for 1 week at 10mM glucose (Affymetrix Rat 230.2 arrays). Results: Culture in either 2-5mM or 30mM instead of 10mM glucose markedly impaired -cell function without affecting islet cell survival. Of ~16000 probe sets reliably detected in islets, ~5000 were significantly regulated at least 1.4-fold by glucose. Analysis of these probe sets with GeneCluster software identified 10 mRNA profiles with unidirectional up- or down-regulation between 2 and 10, 2 and 30, 5 and 10, 5 and 30 or 10 and 30 mM glucose, and 8 complex V-shaped or inverse V-shaped profiles with a nadir or peak level of expression in 5 or 10mM glucose. Analysis of genes belonging to these various clusters with Onto-express and GenMapp software revealed several signaling and metabolic pathways that may contribute to the induction of -cell dysfunction and apoptosis after culture in low or high vs. intermediate glucose concentration. Conclusion: We have identified 18 distinct mRNA profiles of glucose-induced changes in islet gene mRNA levels that should help understanding the mechanisms by which glucose affects -cell survival and function under states of chronic hypo- or hyperglycemia.
Publication Title
Cluster analysis of rat pancreatic islet gene mRNA levels after culture in low-, intermediate- and high-glucose concentrations.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
The aim of the study was to generate transcriptome of wild-type and G9a mutant adult flies (females) 24h post-infection with Drosophila C Virus (DCV). Overall design: We generated 8 different data sets. For wild-type controls and G9a mutants, we performed both mock and DCV infection, and collected both whole flies and fat bodies. All flies were 3-5 days old females.
Publication Title
The epigenetic regulator G9a mediates tolerance to RNA virus infection in Drosophila.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Rattus norvegicus
- 70 Downloadable Samples
- Affymetrix Rat Expression 230A Array (rae230a)
Description
The rat uterus responds to acute estrogen treatment with a series of well characterized physiological responses; however, the gene expression changes required to elicit these responses have not been fully characterized. In order to understand early events induced by estrogen exposure in vivo, we evaluated the temporal gene expression in the uterus of the immature rat after a single dose of 17 Alpha-ethynyl estradiol (EE) by microarray analysis, evaluating the expression of 15,923 genes. Immature 20 day old rats were exposed to a single dose of EE (10 ug/kg) and the effect on uterine histology, weight and gene expression were determined after 1, 2, 8, 24, 48, 72 and 96 h. EE induced changes in the expression of 3,867 genes, at least at one time point (p¡Ü0.0001), and at least 1.5 fold (up- or down-regulated). Specifically, the expression of 8, 116, 3030, 2076, 381, 445, and 125 genes was modified at 1, 2, 8, 24, 48, 72 or 96 hours after exposure to EE respectively (p¡Ü0.0001, t Test). At the tissue and organ level, a clear uterotrophic response was elicited by EE after only 8 h, reaching a maximum after 24 h and remaining detectable even after 96 h of exposure. The uterine phenotypic changes were induced by sequential changes in the transcriptional status of a large number of genes, in a program that involves multiple molecular pathways. Using the gene ontology to better understand the temporal response to estrogen exposure, we determined that the earliest changes were in the expression of genes whose products are involved in transcriptional regulation and signal transduction, followed by genes implicated in protein synthesis, energy utilization, solute transport, cell proliferation and differentiation, tissue remodeling and immunological responses among other pathways. The compendium of genes here presented represents a comprehensive compilation of estrogen-responsive genes involved in the uterotrophic response.
Publication Title
Uterine temporal response to acute exposure to 17alpha-ethinyl estradiol in the immature rat.
Sample Metadata Fields
Sex, Age, Specimen part, Compound, Time
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
We infected Drosophila S2 cells (invitrogen) with Drosophila C virus (DCV) (Multiplicity of Infection = 10), and harvested samples for further analysis at 8 and 24 hours post-infection.
Publication Title
The heat shock response restricts virus infection in Drosophila.
Sample Metadata Fields
Cell line, Time
View Samples
GSE40348- Rattus norvegicus
- 300 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A novel transcriptomics based in vitro method to compare and predict hepatotoxicity based on mode of action.
Sample Metadata Fields
Sex, Time
View Samples- Rattus norvegicus
- 30 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This study provides an evaluation of changes in gene expression associated with dioctyl phthalate treatment of rat hepatocytes in vitro.
Publication Title
A novel transcriptomics based in vitro method to compare and predict hepatotoxicity based on mode of action.
Sample Metadata Fields
Sex, Time
View Samples- Rattus norvegicus
- 30 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This study provides an evaluation of changes in gene expression associated with acetominophen treatment of rat hepatocytes in vitro.
Publication Title
A novel transcriptomics based in vitro method to compare and predict hepatotoxicity based on mode of action.
Sample Metadata Fields
Sex, Time
View Samples