We used microarray analyses in adult female zebrafish (Danio rerio) to identify metabolic pathways regulated by starvation in two key organs that 1) serve biosynthetic and energy mobilizing functions (liver) and 2) consume energy and direct behavioral responses (brain). Starvation affected the expression of 574 transcripts in the liver, indicating an overall decrease in metabolic activity, reduced lipid metabolism, protein biosynthesis and proteolysis, and cellular respiration, and increased gluconeogenesis. Starvation also regulated expression of many components of the Unfolded Protein Response, the first such report in a species other than yeast (Saccharomyces cerevisiae) and mice (Mus musculus). The response of the zebrafish hepatic transcriptome to starvation was strikingly similar to that of rainbow trout (Oncorhynchus mykiss), but very different from common carp (Cyprinus carpio) and mouse. The transcriptome of zebrafish whole brain was much less affected than the liver, with only two differentially expressed genes, both down-regulated. Down-regulation of one of these genes, matrix metalloproteinase 9 (mmp9), suggests increased inhibition of apoptosis (neuroprotection) and decreased restructuring of the extracellular matrix in the brain of starved zebrafish. The low level of response in the transcriptome of whole zebrafish brain agrees with observations that the brain is metabolically protected compared to the rest of the body.
Effect of starvation on transcriptomes of brain and liver in adult female zebrafish (Danio rerio).
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View SamplesThe liver plays a central role in vertebrate glucose homeostasis, and is also one of the most sexually dimorphic organs in terms of gene expression. While the extent of hepatic sexual dimorphism has been well described in mammals, little is known regarding this phenomenon in non-mammalian species, particularly fish. In this study, we examined hepatic gene expression and physiological phenotypes (growth, proximate body composition, retention efficiencies) to determine whether male and female zebrafish respond differently to diets comprised of 0, 15, 25, or 35 % carbohydrate. Using both Affymetrix microarrays and qRTPCR, we observed substantial sexual dimorphism in the hepatic transcriptome, and the response of some genes to dietary carbohydrate manipulation also varied by sex. Males upregulated genes associated with oxidative metabolism, carbohydrate metabolism, energy production, and amelioration of oxidative stress, while females had higher expression levels of genes associated with translation. Males also expressed elevated levels of hnf4a, a gene thought to be involved in regulating hepatic sexual dimorphism in the rodent. Dietary carbohydrate affected hepatic gene expression, growth performance, retention efficiencies of protein and energy, and percentage of moisture, lipid, and ash. Significant diet effects reflected differences between the 0% carbohydrate diet and the other diets, consistent with previous work on other cyprinids showing a high tolerance for dietary carbohydrate. Our data support the use of the zebrafish as a model for the study of both normal and disease states associated with carbohydrate metabolism, and highlight the importance of accounting for both sex and diet
Sexual dimorphism in hepatic gene expression and the response to dietary carbohydrate manipulation in the zebrafish (Danio rerio).
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View SamplesA great number of studies have investigated changes induced by morphine exposure in gene expression using several experimental models. In this study, we examined gene expression changes during chronic exposure to morphine during maturation and differentiation of zebrafish CNS.
Whole-genome expression profile in zebrafish embryos after chronic exposure to morphine: identification of new genes associated with neuronal function and mu opioid receptor expression.
Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cinacalcet inhibits neuroblastoma tumor growth and upregulates cancer-testis antigens.
Specimen part, Treatment
View SamplesCaSR modulation inhibits neuroblastoma growth
Cinacalcet inhibits neuroblastoma tumor growth and upregulates cancer-testis antigens.
Specimen part, Treatment
View SamplesCaSR modulation inhibits neuroblastoma growth
Cinacalcet inhibits neuroblastoma tumor growth and upregulates cancer-testis antigens.
Specimen part, Treatment
View SamplesWe used RNA sequencing to study gene expression in lymph node derived DCs from anaphylactic mice sensitized intranasally with the major peach allergen Pru p 3, during the acute reaction phase, induced intraperitoneally. In total, 237 genes changed significantly, 181 showing at least two-fold changes. Almost three quarters of these increased during anaphylaxis Overall design: 5 Female Balb/c mice aged 4-5 weeks, were sensitized to peach using intranasally administered Pru p 3 in combination with LPS and challenged intraperitoneally as described previously . 5 Littermates, treated with intranasally administered PBS (instead of Pru p 3 and LPS), and later given an intraperitoneal challenge as per the anaphylactic mice, were used for comparison.
Transcriptional Profiling of Dendritic Cells in a Mouse Model of Food-Antigen-Induced Anaphylaxis Reveals the Upregulation of Multiple Immune-Related Pathways.
Sex, Cell line, Treatment, Subject
View SamplesDocetaxel is the standard first line therapy for hormone-refractory prostate cancer patients. Here we generated models of Docetaxel resistance in prostate cancer cells to study the molecular pathways that drive the acquisition of resistance to this therapy. We used microarrays to detail the global program of gene expression underlying the acquisition of Docetaxel resistance in prostate cancer cells.
Suppression of acquired docetaxel resistance in prostate cancer through depletion of notch- and hedgehog-dependent tumor-initiating cells.
Specimen part, Cell line
View SamplesThe combination of defined factors with small molecules targeting epigenetic factors is a strategy that has been shown to enhance optimal derivation of human iPSCs and could be used for therapeutic and regenerative medicine applications. In this study, we showed that a new first-in-class dual G9a/DNMT inhibitor CM272 compound improves the standard four-factor reprogramming efficiency of human fibroblast. The use of CM272 facilitates the generation of iPSC with only two factors, OCT4 and SOX2, allowing the removal of potentially oncogenic factors such as cMYC or KLF4. Taking a closer look at the early events occurring during cell reprogramming we demonstrated that treatment with our G9a/DNMT dual inhibitor induces heterochromatin relaxation, facilitates the engagement of OCT4 and SOX2 transcription factors to the genome and promotes mesenchymal to epithelial transition during cell reprogramming. Thus, the use of this new G9a/DNMT dual inhibitor compound may represent an interesting alternative for improving cell reprogramming.
Reversible dual inhibitor against G9a and DNMT1 improves human iPSC derivation enhancing MET and facilitating transcription factor engagement to the genome.
Sex, Specimen part, Disease, Cell line
View SamplesMechanisms of immune regulation may control proliferation of aberrant plasma cells (PCs) in patients with the asymptomatic monoclonal gammopathy of undetermined significance (MGUS) preventing progression to active multiple myeloma (MM). We investigated the role of CD85j (LILRB1), an inhibitory immune checkpoint for B cell function, in MM pathogenesis.
Loss of the Immune Checkpoint CD85j/LILRB1 on Malignant Plasma Cells Contributes to Immune Escape in Multiple Myeloma.
Specimen part, Cell line
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