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GSE84250
Homo sapiens
12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), (imblegenhumandnamethylation2.1mdeluxepromoterarray[100929hg19deluxeprommethhx1)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Valproic acid (VPA) is a very potent anti-cancer and neuro-protective drug. However, exposure to VPA may cause accumulation of lipids in the liver which could result in the development of steatosis. As VPA is a fatty acid analogue, most of the performed studies focus on inhibition of the mitochondrial b-oxidation pathway as the possible mode of action. However, investigations exploring the contribution of other processes in particular by using whole genome studies in a relevant human liver model are limited. Furthermore, the contribution of gene expression regulation by DNA methylation changes and/or miRNA changes is hardly known. Therefore, in the present study, we investigated the effect of repetitive VPA exposure on primary human hepatocytes (PHH) on whole genome gene expression-, DNA methylation-, and miRNA changes, using microarrays and integrated data analyses. PHH were exposed to a non-cytotoxic dose of 15 mM VPA for 5 days daily thereby inducing accumulation of lipids. Part of the PHH was left untreated for an additional 3 days in order to study the persistence of changes. VPA modulated the expression of a number of nuclear receptors and their target genes, leading to disturbed fatty acid metabolism and - uptake, ultimately leading to accumulation of triglycerides in the liver which is the key event leading to steatosis. Part of the gene expression changes was epigenetically regulated. Furthermore, after terminating the treatment, the expression and DNA methylation changes of several genes remained persistent, indicating a permanent change in the PHH, causing steatosis development to continue and/or making the PHH more sensitive for steatosis development during a subsequent exposure.
Publication Title
Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 45 Downloadable Samples
- Affymetrix Mouse Clariom S Array (clariomsmouse)
Description
We are daily exposed to a multitude of health hazardous airborne particulate matter with notable deposition in the fragile alveolar region of our lungs. Hence, there is a great need for identification and prediction of material-associated diseases, currently hindered due to the lack of in-depth understanding of causal relationships, in particular between acute exposures and chronic symptoms. By applying advanced microscopies and omics to in vitro and in vivo systems, together with in silico molecular modelling, we have here determined that the long-lasting response to a single exposure can originate from the interplay between the newly discovered nanomaterial quarantining and nanomaterial cycling between different lung cell types. This new insight finally allows us to predict the spectrum of lung inflammation associated with materials of interest using only in vitro measurements and in silico modelling potentially relating outcomes to material properties for large number of materials thus boosting safe-by-design-based material development. Because of its profound implications for animal-free predictive toxicology, our work paves the way to a more efficient and hazard-free introduction of numerous new advanced materials into our lives.
Publication Title
Prediction of Chronic Inflammation for Inhaled Particles: the Impact of Material Cycling and Quarantining in the Lung Epithelium.
Sample Metadata Fields
Cell line
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
Illumina HiSeq 2500
Description
The intestine is an organ with exceptionally high rate of cell turnover and perturbations in this process can lead to disease such as cancer or intestinal atrophy. Nutrition is a key factor regulating the intestinal cell turnover and has a profound impact on intestinal volume and cellular architecture. However, how the intestinal equilibrium is maintained in fluctuating dietary conditions is insufficiently understood. By utilizing the Drosophila midgut as a model, we reveal a novel nutrient sensing mechanism coupling stem cell metabolism with stem cell extrinsic growth signal. Our results show that intestinal stem cells (ISCs) employ the hexosamine biosynthesis pathway (HBP) to monitor nutritional status and energy metabolism. Elevated activity of the HBP promotes Warburg effect-like metabolic reprogramming, which is required for the reactivation of ISCs from calorie restriction-induced quiescence. Furthermore, the HBP activity is an essential facilitator for insulin signaling-induced intestinal growth. In conclusion, intestinal stem cell intrinsic nutrient sensing regulates metabolic pathway activities, and defines the stem cell responsiveness to niche-derived growth signals. Overall design: Intestinal mRNA profiles of 7 days old mated females of UAS-mCD8::GFP, hsFLP; tub-GAL4/+; FRT82B tub-GAL80/FRT82B genotype kept in calorie-restriction +/- 0.1M D-acetylglucosamine for 24h.
Publication Title
Stem Cell Intrinsic Hexosamine Metabolism Regulates Intestinal Adaptation to Nutrient Content.
Sample Metadata Fields
Sex, Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Characterization of the underlying genetic defects in patients with a rare and peculiar phenotype is challenging. Here we have utilized whole genome expression profiling, and identified a homozygous germline mutation in the DDB2 gene in a patient with several facial tumors. The feasibility of using blood derived RNA, diminishing costs of the technology, and the limited number of samples needed provide this approach a powerful new tool that may substantially aid in such gene identification efforts.
Publication Title
Blood-derived gene-expression profiling in unravelling susceptibility to recessive disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Acquisition of the lower jaw (mandible) was evolutionarily important for jawed vertebrates. In humans, syndromic craniofacial malformations often accompany jaw anomalies. Hand2 is involved in coordinating the developmental network of mandibles and the oral apparatus through Hand2-downstream genes and is therefore a major determinant of jaw identity.
Publication Title
Specification of jaw identity by the Hand2 transcription factor.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
Both environmental and genetic factors play important roles in the development of the metabolic syndrome. To elucidate how these factors interact under normal conditions, C57Bl/6 (B6) and 129S6/SvEvTac (129) mice were placed on a low-fat or high-fat diet. Liver samples were extracted and hybridized to Affymetrix Genome U74 (version 2) arrays.
Publication Title
Effects of diet and genetic background on sterol regulatory element-binding protein-1c, stearoyl-CoA desaturase 1, and the development of the metabolic syndrome.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
SKBR3 cells expressing NDRG1 shRNA1 or vector control were harvested by trypsinization and total RNA was extracted. Silencing NDRG1 reduces cell proliferation rates, causing lipid metabolism dysfunction including increased fatty acid incorporation into neutral lipids and lipid droplets.
Publication Title
NDRG1 regulates neutral lipid metabolism in breast cancer cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In mouse, spermatogonial stem/progenitor cells are the progenitor cell which develop to mature sperms through a series of mitotic and meiotic divisions and differentiation. Gfra1 is an established surface marker for mouse spermatogonial stem/progenitor cells. In this study, we used a transcriptomic approach to investigate the effect of aging on Gfra1-positive and -negative populations of mouse male germ cells.
Publication Title
Age affects gene expression in mouse spermatogonial stem/progenitor cells.
Sample Metadata Fields
Sex, Age
View Samples- Saccharomyces cerevisiae
- 16 Downloadable Samples
- Affymetrix Yeast Genome S98 Array (ygs98)
Description
Sucrose is a major carbon source for industrial bioethanol production by Saccharomyces cerevisiae. In yeasts, two modes of sucrose metabolism occur: (i) extracellular hydrolysis by invertase, followed by uptake and metabolism of glucose and fructose, and (ii) uptake via sucrose-H+ symport followed by intracellular hydrolysis and metabolism. Although alternative start codons in the SUC2 gene enable synthesis of extracellular and intracellular invertase isoforms, sucrose hydrolysis in S. cerevisiae predominantly occurs extracellularly. In anaerobic cultures, intracellular hydrolysis theoretically enables a 9 % higher ethanol yield than extracellular hydrolysis, due to energy costs of sucrose-proton symport. This prediction was tested by engineering the promoter and 5 coding sequences of SUC2, resulting in relocation of invertase to the cytosol. In anaerobic sucrose-limited chemostats, this iSUC2-strain showed an only 4% increased ethanol yield and high residual sucrose concentrations indicated suboptimal sucrose-transport kinetics. To improve sucrose-uptake affinity, it was subjected to 95 generations of anaerobic, sucrose-limited chemostat cultivation, resulting in a 20-fold decrease of residual sucrose concentrations and a 10-fold increase of the sucrose-transport capacity. A single-cell isolate showed an 11 % higher ethanol yield on sucrose in chemostat and batch cultures than an isogenic SUC2 reference strain, while transcriptome analysis revealed elevated expression of AGT1, encoding a disaccharide-proton symporter, and other maltose-related genes. Deletion of AGT1, which had been duplicated during laboratory evolution, restored the growth characteristics of the unevolved iSUC2 strain. This study demonstrates that engineering the topology of sucrose metabolism is an attractive strategy to improve ethanol yields in industrial processes.
Publication Title
Increasing free-energy (ATP) conservation in maltose-grown Saccharomyces cerevisiae by expression of a heterologous maltose phosphorylase.
Sample Metadata Fields
No sample metadata fields
View Samples