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GSE94521
Homo sapiens
57 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The in vitro test battery of the European research consortium ESNATS (novel stem cell-based test systems) has been used to screen for potential human developmental toxicants. As part of this effort, the migration of neural crest (MINC) assay has been used to evaluate chemical effects on neural crest function. It identified some drug-like compounds in addition to known environmental toxicants. The hits included the HSP90 inhibitor geldanamycin, the chemotherapeutic arsenic trioxide, the flame-retardant PBDE-99, the pesticide triadimefon and the histone deacetylase inhibitors valproic acid and trichostatin A. Transcriptome changes triggered by these substances in human neural crest cells were recorded and analysed here to answer three questions: (1) can toxicants be individually identified based on their transcript profile; (2) how can the toxicity pattern reflected by transcript changes be compacted/ dimensionality-reduced for practical regulatory use; (3) how can a reduced set of biomarkers be selected for large-scale follow up? Transcript profiling allowed clear separation of different toxicants and the identification of toxicant types in a blinded test study. We also developed a diagrammatic system to visualize and compare toxicity patterns of a group of chemicals by giving a quantitative overview of altered superordinate biological processes (e.g. activation of KEGG pathways or overrepresentation of gene ontology terms). The transcript data were mined for potential markers of toxicity, and 39 transcripts were selected to either indicate general developmental toxicity or distinguish compounds with different modes-of-action in read-across. In summary, we found inclusion of transcriptome data to largely increase the information from the MINC phenotypic test.
Publication Title
Identification of transcriptome signatures and biomarkers specific for potential developmental toxicants inhibiting human neural crest cell migration.
Sample Metadata Fields
Sex, Specimen part
View Samples- Saccharomyces cerevisiae
- 10 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
Background
Publication Title
Distinct roles of the Gcn5 histone acetyltransferase revealed during transient stress-induced reprogramming of the genome.
Sample Metadata Fields
Treatment
View Samples- Rattus norvegicus
- 15 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
OBJECTIVE: To analyze genome-wide changes in chondrocyte gene expression in a surgically induced model of early osteoarthritis (OA) in rats, to assess the similarity of this model to human OA, and to identify genes and mechanisms leading to OA pathogenesis. METHODS: OA was surgically induced in 5 rats by anterior cruciate ligament transection and partial medial meniscectomy. Sham surgery was performed in 5 additional animals, which were used as controls. Both groups underwent 4 weeks of forced mobilization, 3 times per week. RNA was extracted directly from articular chondrocytes in the OA (operated), contralateral, and sham-operated knees. Affymetrix GeneChip expression arrays were used to assess genome-wide changes in gene expression. Expression patterns of selected dysregulated genes, including Col2a1, Mmp13, Adamts5, Ctsc, Ptges, and Cxcr4, were validated by real-time polymerase chain reaction, immunofluorescence, or immunohistochemistry 2, 4, and 8 weeks after surgery. RESULTS: After normalization, comparison of OA and sham-operated samples showed 1,619 differentially expressed probe sets with changes in their levels of expression >/=1.5-fold, 722 with changes >/=2-fold, 135 with changes >/=4-fold, and 20 with changes of 8-fold. Dysregulated genes known to be involved in human OA included Mmp13, Adamts5, and Ptgs2, among others. Several dysregulated genes (e.g., Reln, Phex, and Ltbp2) had been identified in our earlier microarray study of hypertrophic chondrocyte differentiation. Other genes involved in cytokine and chemokine signaling, including Cxcr4 and Ccl2, were identified. Changes in gene expression were also observed in the contralateral knee, validating the sham operation as the appropriate control. CONCLUSION: Our results demonstrate that the animal model mimics gene expression changes seen in human OA, supporting the relevance of newly identified genes and pathways to early human OA. We propose new avenues for OA pathogenesis research and potential targets for novel OA treatments, including cathepsins and cytokine, chemokine, and growth factor signaling pathways, in addition to factors controlling the progression of chondrocyte differentiation.
Publication Title
Global analyses of gene expression in early experimental osteoarthritis.
Sample Metadata Fields
No sample metadata fields
View Samples- Saccharomyces cerevisiae
- 10 Downloadable Samples
- Affymetrix Yeast Genome 2.0 Array (yeast2)
Description
The data provide information expression profile in yeast for 5 different physioloigcal conditions during stress adpatation and stress recovery (normal growth, during stress adaptation, after stress adaptation, under stress recovery, after stress recovery) in yeast. The purpose of the study is to understand how histone acetyltransferase HATs (Gcn5) apply it is function in gene regulation by changing global or local histone acetylation level under different physiological conditions.
Publication Title
Distinct roles of the Gcn5 histone acetyltransferase revealed during transient stress-induced reprogramming of the genome.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
MicroRNAs establish robustness and adaptability of a critical gene network to regulate progenitor fate decisions during cortical neurogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 11 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
During cortical development neurons are generated sequentially from basal progenitors (BPs) which specifically express the transcription factor Tbr2. We used fluorescent-activaed cell sorting (FACS) to isolate BPs from Tbr2GFP knockin reporter mice (Arnold SJ et al. Genesis, 2009) at early (embryonic day, E13) and late (embryonic day, E16) stages of cortical neurogenesis and determined mRNA expression profiles using mouse mRNA microarray (Illumina MouseWG-6 v2). Comparison of E13 and E16 mRNA expression profiles allowed us to identify regulatory gene networks for maintaining stage specific homeostasis of BPs throughout neurogenesis.
Publication Title
MicroRNAs establish robustness and adaptability of a critical gene network to regulate progenitor fate decisions during cortical neurogenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Protein synthesis belongs to the most energy consuming processes in the cell. Lowering oxygen tension below normal (hypoxia) causes a rapid inhibition of global mRNA translation due to the decreased availability of energy. Interestingly, subsets of mRNAs pursue active translation under such circumstances. In human fibrosarcoma cells (HT1080) exposed to prolonged hypoxia (36 h, 1% oxygen) we observed that transcripts are either increasingly or decreasingly associated with ribosomes localized at the endoplasmic reticulum (ER). In a global setting it turned out that only 31% of transcripts showing elevated total-RNA levels were also increasingly present at the ER in hypoxia. These genes, regulated by its expression as well as its ER-localization, belong to the gene ontologys hypoxia response, glycolysis and HIF-1 transcription factor network supporting the view of active mRNA translation at the ER during hypoxia. Interestingly, a large group of RNAs was found to be unchanged at the expression level, but translocate to the ER in hypoxia. Among these are transcripts encoding translation factors and >180 ncRNAs. In summary, we provide evidence that protein synthesis is favoured at the ER and, thus, partitioning of the transcriptome between cytoplasmic and ER associated ribosomes mediates adaptation of gene expression in hypoxia.
Publication Title
Hypoxia-induced gene expression results from selective mRNA partitioning to the endoplasmic reticulum.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 21 Downloadable Samples
Illumina HiSeq 2500
Description
AGRP neurons are a hypothalamic population that senses physiological energy deficit and consequently increases appetite. Molecular and cellular processes for energy-sensing and elevated neuronal output are critical for understanding the central nervous system response to energy deficit states, such as during weight-loss. Cell type-specific transcriptomics can be used to identify pathways that counteract weight-loss but, in adult mice, this has been limited by technical challenges. We report high-quality gene expression profiles of AGRP neurons under well-fed and energy deficit states. For comparison, we also analyzed POMC neurons, an intermingled population that suppresses appetite. This data newly identifies cell type-selective involvement of signaling pathways, ion channels, neuropeptides, and G-protein coupled receptors. Combined with methods to validate and manipulate these pathways, this resource greatly expands molecular insight into neuronal regulation of body weight, and may be useful for devising therapeutic strategies for obesity and eating disorders. Overall design: Examination of 2 different neuronal cell types under 2 conditions.
Publication Title
Cell type-specific transcriptomics of hypothalamic energy-sensing neuron responses to weight-loss.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 15 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Pharmaceutical chemicals used in human medicine are released into surface waters via municipal effluents and pose a risk for aquatic organisms. Among these substances are selective serotonin reuptake inhibitors (SSRIs) which can affect aquatic organisms at sub ppb concentrations. To better understand biochemical pathways influenced by SSRIs, evaluate changes in the transcriptome, and identify gene transcripts with potential for biomarkers of exposure to SSRIs; larval zebrafish Danio rerio were exposed (96 h) to two concentrations (25 and 250 g/L) of the SSRIs, fluoxetine and sertraline, and changes in global gene expression were evaluated (Affymetrix GeneChip Zebrafish Array). Significant changes in gene expression (>=1.7 fold change, p<0.05) were determined with Partek Genomics Suite Gene Expression Data Analysis System and ontology analysis was conducted using Molecular Annotation System 3. The number of genes differentially expressed after fluoxetine exposure was 288 at 25 g/L and 131 at 250 g/L; and after sertraline exposure was 33 at 25 g/L and 52 at 250 g/L. Five genes were differentially regulated in all treatments relative to control, suggesting that both SSRIs share some similar molecular pathways. Among them, expression of the gene coding for FK506 binding protein 5 (FKBP5), which is annotated to stress response regulation, was highly down-regulated in all treatments (results confirmed by qRT-PCR). Gene ontology analysis indicated that regulation of stress response and cholinesterase activity were critical functions influenced by these SSRIs, and suggested that changes in the transcription of FKBP5 or acetylcholinesterase could be useful biomarkers of SSRIs exposure in wild fish.
Publication Title
Global gene expression in larval zebrafish (Danio rerio) exposed to selective serotonin reuptake inhibitors (fluoxetine and sertraline) reveals unique expression profiles and potential biomarkers of exposure.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Metastatic colonization involves cancer cell lodgment or adherence in the microvasculature and subsequent migration of those cells across the endothelium into a secondary organ site. To study this process further, we analyzed transendothelial migration of human PC-3 prostate cancer cells in vitro. We isolated a subpopulation of cells, TEM4-18, that crossed an endothelial barrier more efficiently, but surprisingly, were less invasive than parental PC-3 cells in other contexts in vitro. Importantly, TEM4-18 cells were more aggressive than PC-3 cells in a murine metastatic colonization model. Microarray and FACS analysis of these cells showed that the expression of many genes previously associated with leukocyte trafficking and cancer cell extravasation were either unchanged or down-regulated. TEM4-18 cells exhibited characteristic molecular markers of an epithelial-to-mesenchymal transition (EMT), including frank loss of E-cadherin expression and upregulation of the E-cadherin repressor ZEB1. Silencing ZEB1 in TEM4-18 cells resulted in increased E-cadherin and reduced transendothelial migration. TEM4-18 cells also express N-cadherin, which was found to be necessary, but not sufficient for increased transendothelial migration. Our results extend the role of EMT in metastasis to transendothelial migration and implicate ZEB1 and N-cadherin in this process in prostate cancer cells.
Publication Title
ZEB1 enhances transendothelial migration and represses the epithelial phenotype of prostate cancer cells.
Sample Metadata Fields
No sample metadata fields
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