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GSE58893
Homo sapiens
12 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Systemic delivery of a miR34a mimic as a potential therapeutic for liver cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To identify direct tumor mRNA targets of miR-34a, tumor RNAs isolated from whole tumors from animals treated with negative control and MRX34
Publication Title
Systemic delivery of a miR34a mimic as a potential therapeutic for liver cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina Genome Analyzer IIx, Illumina HiSeq 2000
Description
We report liver transcript profiling by RNA sequencing of Atp7b-/- and wild type mice at six weeks of age. Transcriptional network analysis of RNA-seq data reveals a highly interconnected network of transcriptional activators with over-representation of zinc-dependent and zinc-responsive transcription factors. Overall design: Wild type and Atp7b-/- Mice were maintained on strain C57BL x 129S6/SvEv. Housing was in shoebox cages and fed Mazuri Rodent diet (PMI Nutrition, Inc., Richmond, Indiana), containing 16 ppm Cu, 100 ppm Zn, and 235 ppm Fe and water ad libitum, with a 12-hour light/dark cycle. Six-week-old mice of both sexes were used for transcriptomic studies. Animals were sacrificed by carbon dioxide asphyxiation and liver tissue was harvested for RNA isolation. RNA sequencing was performed at the National Center for Genome Resources (NCGR) using the GAIIx platform. Average read quality was 38. An initial dataset was generated using two wild type and two Atp7b-/- samples with singleton 1x54 runs with 15,823,058; 8,149,631; 22,931,967 and 9,538,147 reads. A second paired end (2x54) dataset was generated to augment the initial singleton dataset with one wild type and one Atp7b-/- run resulting in 36,360,686 and 38,366,743 reads, respectively.
Publication Title
Altered zinc balance in the Atp7b<sup>-/-</sup> mouse reveals a mechanism of copper toxicity in Wilson disease.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
- IlluminaHiSeq2000
Description
Background: E-cadherin is an adherens junction protein that forms homophilic intercellular contacts in epithelial cells while also interacting with the intracellular cytoskeletal networks. It has roles including establishment and maintenance of cell polarity, differentiation, migration and signalling in cell proliferation pathways. Its downregulation is commonly observed in epithelial tumours and is a hallmark of the epithelial to mesenchymal transition (EMT). Methods: To improve our understanding of how E-cadherin loss contributes to tumorigenicity, we investigated the impact of its elimination from the non-tumorigenic breast cell line MCF10A. We performed cell-based assays and whole genome RNAseq to characterize an isogenic MCF10A cell line that is devoid of CDH1 expression due to an engineered homozygous 4bp deletion in CDH1 exon 11. Results: The E-cadherin-deficient line, MCF10A CDH1-/- showed subtle morphological changes, weaker cell-substrate adhesion, delayed migration, but retained cell-cell contact, contact growth inhibition and anchorage-dependent growth. Within the cytoskeleton, the apical microtubule network in the CDH1-deficient cells lacked the radial pattern of organization present in the MCF10A cells and F-actin formed thicker, more numerous stress fibres in the basal part of the cell. Whole genome RNAseq identified compensatory changes in the genes involved in cell-cell adhesion while genes involved in cell-substrate adhesion, notably ITGA1, COL8A1, COL4A2 and COL12A1, were significantly downregulated. Key EMT markers including CDH2, FN1, VIM and VTN were not upregulated although increased expression of proteolytic matrix metalloprotease and kallikrein genes was observed. Conclusions: Overall, our results demonstrated that E-cadherin loss alone was insufficient to induce an EMT or enhance transforming potential in the non-tumorigenic MCF10A cells but was associated with broad transcriptional changes associated with tissue remodelling. Overall design: Examination of the impact of E-cadherin (CDH1) loss in an isogenic pair of breast cell lines.
Publication Title
E-cadherin loss alters cytoskeletal organization and adhesion in non-malignant breast cells but is insufficient to induce an epithelial-mesenchymal transition.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 19 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Diabetic Neuropathy (DN) is a common complication of diabetes. Currently, there is no drug treatment to prevent or slow the development of DN. Rosiglitazone (Rosi) is a potent insulin sensitizer and may also slow the development of DN by a mechanism independent of its effect on hyperglycemia. A two by two design was used to test the effect of Rosi treatment on the development of DN. Streptozotocin-induced diabetic DBA/2J mice were treated with Rosi. DN and oxidative stress were quantified, and gene expression was profiled using the Affymetrix Mouse Genome 430 2.0 microarray platform. An informatics approach identified key regulatory elements activated by Rosi. Diabetic DBA/2J mice developed severe hyperglycemia, DN and elevated oxidative stress. Rosi treatment did not affect hyperglycemia but did reduce oxidative stress and prevented development of thermal hypoalgesia. Two novel transcription factor binding modules were identified that may control genes correlated to changes in DN following Rosi treatment: SP1F_ZBPF and EGRF_EGRF. Rosi treatment reduced oxidative stress and DN independent of its insulin sensitizing effects. Gene expression profiling identified two novel targets activated by Rosi treatment. These targets may be useful in designing drugs with the same efficacy as Rosi in treating DN but with fewer undesirable effects.
Publication Title
Rosiglitazone treatment reduces diabetic neuropathy in streptozotocin-treated DBA/2J mice.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Arabidopsis thaliana
- 18 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
We isolated mutants in Arabidopsis with enhanced ambient temperature response. Microarray analysis was performed to understand the extent to which ambient temperature transcriptome is perturbed in the mutants in comparison with the WT at non inductive 12 C and after shift to inductive 27 C for 2 h and 24 h.
Publication Title
H2A.Z-containing nucleosomes mediate the thermosensory response in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 35 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Through post-transcriptional regulation of gene expression, miRNAs affect numerous regulatory pathways including those crucial for maintaining metabolic balance. Here we demonstrate that a neuronal-specific inhibition of miRNA maturation in adult mice leads to a rapid development of severe obesity, which is equally rapidly reversed. Development of obesity was associated with increased food intake and efficiency, and decreased locomotor activity. The ensuing decrease in body weight resembled a catabolic state with lowered O2-consumption and respiratory-exchange ratio. Brain transcriptome analyses in obese mice identified several obesity-related pathways including leptin, somatostatin, and nemo-like kinase signaling, as well as genes involved in feeding and appetite (e.g. Pmch, Neurotensin). A cluster of genes involved in synaptic plasticity was specifically enriched in post-obese mice that did not appear in obese mice. While other studies have identified a role for miRNAs in obesity our model is unique in that it allows for the study of processes involved in reversing obesity.
Publication Title
A neuron-specific deletion of the microRNA-processing enzyme DICER induces severe but transient obesity in mice.
Sample Metadata Fields
Specimen part, Time
View Samples- Arabidopsis thaliana
- 18 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Response to photoperiod in Arabidopsis wildtype, co, and ft mutant plants.
Publication Title
Integration of spatial and temporal information during floral induction in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 14 Downloadable Samples
- NextSeq 500
Description
Plants are sessile organisms and therefore must sense and respond to changes of their surrounding conditions such as ambient temperature, which vary diurnally and seasonally. It is not yet clear how plants sense temperature and integrate this information into their development. We have previously shown that H2A.Z-nucleosomes are evicted in response to warmer temperatures. It is not clear however, whether the link between transcriptional responsiveness and changes in H2A.Z binding in context of temperature shifts is a global trend that can be seen throughout the genome, or the phenomenon is specific to a specialised set of temperature-responsive genes. In addition to the role of H2A.Z-nucleosome dynamics in the transcriptional response to temperature, it was shown that genes strongly misregulated in the h2a.z mutant are enriched for gene categories involved in response to multiple environmental cues. This suggests that H2A.Z could be implicated in the transcriptional response to various environmental inputs, raising the question: What brings the specificity of H2A.Z dynamics in response to temperature? To address this question we have profiled H2A.Z-nucleosome occupancy genome wide (using ChIP-seq) during a time course after temperature variation and compared its dynamics to transcriptional changes. We identified a fast, targeted and transient eviction of H2A.Z associated with transcriptional activation in response to temperature for a few hundreds genes. This eviction is associated with a reduction of the stability of the nucleosome. Moreover the genes with a fast H2A.Z eviction were strongly enriched in heat shock elements in their promoter and we observed a strong association between HSF1 binding and H2AZ eviction at warm temperature. These results highlight the importance of the interplay between transcription factors and chromatin to allow a controlled and dynamics response to temperature. Overall design: RNA-seq were generated in duplicate for seedlings shifted to warm temperature
Publication Title
Transcriptional Regulation of the Ambient Temperature Response by H2A.Z Nucleosomes and HSF1 Transcription Factors in Arabidopsis.
Sample Metadata Fields
Subject
View Samples- Arabidopsis thaliana
- 2 Downloadable Samples
- Illumina HiSeq 1000
Description
Plants are sessile organisms and therefore must sense and respond to changes of their surrounding conditions such as ambient temperature, which vary diurnally and seasonally. It is not yet clear how plants sense temperature and integrate this information into their development. We have previously shown that H2A.Z-nucleosomes are evicted in response to warmer temperatures. It is not clear however, whether the link between transcriptional responsiveness and changes in H2A.Z binding in context of temperature shifts is a global trend that can be seen throughout the genome, or the phenomenon is specific to a specialised set of temperature-responsive genes. In addition to the role of H2A.Z-nucleosome dynamics in the transcriptional response to temperature, it was shown that genes strongly misregulated in the h2a.z mutant are enriched for gene categories involved in response to multiple environmental cues. This suggests that H2A.Z could be implicated in the transcriptional response to various environmental inputs, raising the question: What brings the specificity of H2A.Z dynamics in response to temperature? To address this question we have profiled H2A.Z-nucleosome occupancy genome wide (using ChIP-seq) during a time course after temperature variation and compared its dynamics to transcriptional changes. We identified a fast, targeted and transient eviction of H2A.Z associated with transcriptional activation in response to temperature for a few hundreds genes. This eviction is associated with a reduction of the stability of the nucleosome. Moreover the genes with a fast H2A.Z eviction were strongly enriched in heat shock elements in their promoter and we observed a strong association between HSF1 binding and H2AZ eviction at warm temperature. These results highlight the importance of the interplay between transcription factors and chromatin to allow a controlled and dynamics response to temperature. Overall design: RNA-seq were generated in duplicate for seedlings shifted to warm temperature
Publication Title
Transcriptional Regulation of the Ambient Temperature Response by H2A.Z Nucleosomes and HSF1 Transcription Factors in Arabidopsis.
Sample Metadata Fields
Subject
View Samples