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GSE73739
Danio rerio
6 Downloadable Samples
Zebrafish Gene 1.0 ST Array (zebgene10st)
Description
Microcystin-LR (MC-LR), the most toxic member of microcystin family, inhibits protein phosphatase PP2A, triggers oxidative stress and induces hepatotoxicity. Gene expression profiling of MC-LR treated larvae using DNA microarray analysis revealed effects in the retinal visual cycle and pigmentation synthesis pathways that have not been previously associated with MC-LR. Liver-related genes were also differentially expressed. The microarray data were confirmed by quantitative real-time PCR. Our findings provide new evidence that microcystin-LR exposure of zebrafish larvae modulates the retinal visual cycle and pigmentation synthesis pathways and ultimately alter larval zebrafish behavior
Publication Title
Transcriptional and Behavioral Responses of Zebrafish Larvae to Microcystin-LR Exposure.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 38 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are the most common treatment for major depression. However, approximately 50% of depressed patients fail to achieve an effective treatment response. Understanding how gene expression systems relate to treatment responses may be critical for understanding antidepressant resistance. Transcriptome profiling allows for the simultaneous measurement of expression levels for thousands of genes and the opportunity to utilize this information to determine mechanisms underlying antidepressant treatment responses. However, the best way to relate this immense amount of information to treatment resistance remains unclear. We take a novel approach to this question by examining dentate gyrus transcriptomes from the perspective of a stereotyped fluoxetine-induced gene expression program. Expression programs usually represent stereotyped changes in expression levels that occur as cells transition phenotypes. Fluoxetine will shift transcriptomes so they lie somewhere between a baseline state and a full-response at the end of the program. The position along this fluoxetine-induced gene expression program (program status) was measured using principal components analysis (PCA). The same expression program was initiated in treatment-responsive and resistant mice but treatment response was associated with further progression along the fluoxetine-induced gene expression program. The study of treatment-related differences in gene expression program status represents a novel way to conceptualize differences in treatment responses at a transcriptome level. Understanding how antidepressant-induced gene expression program progression is modulated represents an important area for future research and could guide efforts to develop novel augmentation strategies for antidepressant treatment resistant individuals.
Publication Title
Global state measures of the dentate gyrus gene expression system predict antidepressant-sensitive behaviors.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Xenopus laevis
- 6 Downloadable Samples
- Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
The transcription factors Mixer and Sox17beta have well characterized roles in endoderm specification during Xenopus embryogenesis. In order to more thoroughly understand the mechanisms by which these endodermal regulators act, we expressed Mixer and Sox17beta in nave ectodermal tissue and, using oligonucleotide-based microarrays, compared their genomic transcriptional profile to that of unaffected tissue. Using this novel approach, we identified 71 transcripts that are upregulated by Mixer or Sox17beta, 63 of which have previously uncharacterized roles in endoderm development. Furthermore, an in situ hybridization screen using antisense probes for several of these clones identified six targets of Mixer and/or Sox17beta that are expressed in the endoderm during gastrula stages, providing new and regional markers of the endoderm. Our results contribute further insight into the functions of Mixer and Sox17beta and bring us closer to understanding at the molecular level the pathways that regulate endoderm development.
Publication Title
Genomic profiling of mixer and Sox17beta targets during Xenopus endoderm development.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The Affymetrix Human Genome U133 Plus 2.0 Array was used to examine the Genome wide transcriptional changes which follow the treatment of AML xenografts with either PBS control or combination of decitabine (DAC) and cytarabine (Ara-C). Animals were treated with PBS, DAC alone, Ara-C alone, DAC and Ara-C combined (D+A), DAC followed by Ara-C (D/A) or Ara-C followed by DAC (A/D).
Publication Title
Sequential treatment with cytarabine and decitabine has an increased anti-leukemia effect compared to cytarabine alone in xenograft models of childhood acute myeloid leukemia.
Sample Metadata Fields
Specimen part, Disease
View Samples- Homo sapiens
- 16 Downloadable Samples
IlluminaHiSeq2000
Description
Staphylococcus aureus can cause serious skin, respiratory, and other life-threatening invasive infections in humans, and methicillin-resistant S. aureus (MRSA) strains have been acquiring increasing antibiotic resistance. While MRSA was once mainly considered a hospital-acquired infection, the emergence of new strains, some of which are pandemic, has resulted in community-acquired MRSA infections that often present as serious skin infections in otherwise healthy individuals. Accordingly, defining the mechanisms that govern the activation and regulation of the immune response to MRSA is clinically important and could lead to the discovery of much needed rational targets for therapeutic intervention. Because the cytokine thymic stromal lymphopoetin (TSLP) is highly expressed by keratinocytes of the skin3, we investigated its role in host-defense against MRSA. Here we demonstrate that TSLP acts on neutrophils to increase their killing of MRSA. In particular, we show that both mouse and human neutrophils express functional TSLP receptors. Strikingly, TSLP enhances mouse neutrophil killing of MRSA in both an in vitro whole blood killing assay and an in vivo skin infection model. Similarly, TSLP acts directly on purified human blood neutrophils to reduce MRSA burden. Unexpectedly, we demonstrate that TSLP mediates these effects both in vivo and in vitro by engaging the complement C5 system. Thus, TSLP increases MRSA killing in a neutrophil- and complement-dependent manner, revealing a key connection between TSLP and the innate complement system, with potentially important therapeutic implications for control of MRSA infection. Overall design: mRNA expression analysis. 16 samples are from 2 donors, 8 samples per donor, 2 time points (4hr and 16 hr), and 4 conditions (control, TSLP treated, Heat Killed MRSA treated, and TSLP+HKM treated) .
Publication Title
A TSLP-complement axis mediates neutrophil killing of methicillin-resistant <i>Staphylococcus aureus</i>.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 1500
Description
RNAseq analysis was conducted to complement the targeted and untargeted metabolomics analysis of livers overexpressing the CoA-degrading enzyme Nudt7 or GFP (control). Lipid metabolism requires coenzyme A (CoA), which is found in multiple subcellular compartments including the peroxisomes. In the liver, CoA levels are dynamically adjusted between the fed and fasted states. The elevation in CoA levels that occurs during fasting is driven by increased synthesis but also correlates with decreased expression of Nudt7, the major CoA-degrading enzyme in the liver. Nudt7 resides in the peroxisomes and we overexpressed this enzyme in mouse livers to determine its effect on the size and composition of the hepatic CoA pool in the fed and fasted states. Nudt7 overexpression did not change total CoA levels but decreased the concentration of short-chain acyl-CoAs and choloyl-CoA in fasted livers, when endogenous Nudt7 activity was lowest. The effect on these acyl-CoAs correlated with a significant decrease in the hepatic bile acid content and in the rate of peroxisomal fatty acid oxidation, as estimated by targeted and untargeted metabolomics, combined with the measurement of fatty acid oxidation in intact hepatocytes. Identification of the CoA species and metabolic pathways affected the overexpression on Nudt7 in vivo supports the conclusion that the nutritionally-driven modulation of Nudt7 activity could contribute to the regulation of the peroxisomal CoA pool and peroxisomal lipid metabolism. Overall design: Liver mRNA profiles of 4 mice injected with adeno-associated virus to overexpress Nudt7 and 4 mice injected with adeno-associated virus to overexpress GFP (control) were generated by RNAseq using Illumina HiSeq1500
Publication Title
Overexpression of Nudt7 decreases bile acid levels and peroxisomal fatty acid oxidation in the liver.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Vascular hypoperfusion is a pathological phenomenon in the glaucomatous optic nerve head. We report transcriptional responses in GFAP-negative LC cells exposed to in-vitro hypoxic stress (1%O2).
Publication Title
Hypoxia regulated gene transcription in human optic nerve lamina cribrosa cells in culture.
Sample Metadata Fields
Specimen part
View Samples- Zea mays
- 85 Downloadable Samples
- Illumina HiSeq 2500
Description
Analysis of the maize alternative splicing landscape, including transcript discovery and mapping of genotype-dependent variations in alternative splicing using B73, Mo17 and the SX19 inbred mapping population Overall design: Total RNA was isolated from 5 week old leaves of hydroponically grown maize plants and used to construct RNA seq libraries
Publication Title
Genome-wide analysis of alternative splicing in Zea mays: landscape and genetic regulation.
Sample Metadata Fields
Subject
View Samples- Rattus norvegicus
- 59 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
U.S. Service Members and civilians are at risk of exposure to a variety of environmental health hazards throughout their normal duty activities and in industrial occupations. Metals are widely used in large quantities in a number of industrial processes and are a common environmental toxicant, which increases the possibility of being exposed at toxic levels. While metal toxicity has been widely studied, the exact mechanisms of toxicity remain unclear. In order to further elucidate these mechanisms and identify candidate biomarkers, rats were exposed via a single intraperitoneal injection to three concentrations of CdCl2 and Na2Cr2O7, with livers harvested at 1, 3, or 7 days after exposure. Cd and Cr accumulated in the liver at 1 day post exposure. Cd levels remained elevated over the length of the experiment, while Cr levels declined. Metal exposures induced ROS, including hydroxyl radical (OH), resulting in DNA strand breaks and lipid peroxidation. Interestingly, ROS and cellular damage appeared to increase with time post-exposure in both metals, despite declines in Cr levels. Differentially expressed genes were identified via microarray analysis. Both metals perturbed gene expression in pathways related to oxidative stress, metabolism, DNA damage, cell cycle, and inflammatory response. This work provides insight into the temporal effects and mechanistic pathways involved in acute metal intoxication, leading to the identification of candidate biomarkers.
Publication Title
Temporal changes in rat liver gene expression after acute cadmium and chromium exposure.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 49 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Gene expression patterns related to osteogenic differentiation of bone marrow-derived mesenchymal stem cells during ex vivo expansion.
Sample Metadata Fields
No sample metadata fields
View Samples