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Mus musculus
18 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The basic helix-loop-helix (bHLH) transcription factors of the Drosophilas atonal-related superfamily Neurogenin3 (Neurog3) and NeuroD1 promote endocrine differentiation in the gastrointestinal tract. Atonal Homolog 8 (Atoh8/Math6) is a newly identified member of the atonal-related family whose expression is induced by Neurog3 and NeuroD1 in cell culture, indicating a possible role for this gene in the endocrine differentiation program downstream of these two pro-endocrine factors. Intriguingly, available experimental evidence based on a reduced number of genes suggests that Atoh8 may negatively regulate Neurog3-targeting events. In this study, we have analyzed global changes in gene expression profiles upon exogenous expression of Atoh8 alone or in combination with Neurog3 in mouse pancreatic duct (mPAC) cells. These cells activate neuroendocrine-specific gene expression in response to Neurog3 and NeuroD1 and thus serve as an optimal model to evaluate the proendocrine activity of Atoh8. We have compared transcriptional profiles between mPAC cells treated with a recombinant adenovirus expressing Atoh8 (Ad-Atoh8) or a control adenovirus encoding B-galactosidase (Ad-Bgal), and between cells treated with Ad-Neurog3+Ad-Bgal or cells treated with Ad-Neurog3+Ad-Atoh8. The results obtained show that Atoh8 exhibits a very modest transcriptional activity in these cells thus confirming that Atoh8 does not function as a proendocrine gene. Furthermore, our data also confirm the ability of Atoh8 to block Neurog3-dependent transcriptional activation events. However, since repression is only seen for a small subset of Neurog3 gene targets, we discard a general role of Atoh8 as a negative regulator of Neurog3 pro-endocrine activity.
Publication Title
Characterization of the transcriptional activity of the basic helix-loop-helix (bHLH) transcription factor Atoh8.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Relative beta cell deficit and increased beta cell apoptosis are hallmarks of type 2 diabetes (T2D). The Insulin/Insulin Growth Factor (Igf) signaling pathway is an established regulator of beta cell survival and is found downregulated in human T2D islets. The Insulin Receptor Substrate 2 (Irs2) plays a central role in the coordination of this pathway in beta cells. Thus, Irs2 knockout mice (Irs2 -/-) exhibit increased beta cell apoptosis that leads to a progressive decline of beta cell mass and hyperglycaemia. In this study, we sought to determine whether the anti-diabetic compound sodium tungstate could prevent the onset of diabetes in Irs2 -/- mice. Oral administration of tungstate resulted in an overall improvement in whole-body glucose tolerance in Irs2 -/- mice which correlated with increased beta cell mass. Enhanced beta cell mass was due to a dramatic reduction of beta cell apoptosis without changes in proliferation. Whole genome gene profiling analysis of islets isolated from treated Irs2 -/- mice confirmed a broad impact of tungstate on cell death pathways. Mechanistically, tungstate induced Erk1/2 phosphorylation in islets in vitro and, in agreement, treated Irs2 -/- islets exhibited increased basal Erk1/2 phosphorylation. Tungstate also downregulated expression of apoptosis-related genes in Irs2-/- islets in vitro, uncovering a direct effect of this compound in islets. All together, our data demonstrate that tungstate can restore beta cell mass and glucose homeostasis in a context of deficient Insulin/Igf signaling. This study underscores the importance of developing strategies specifically designed to arrest beta cell apoptosis as a means to prevent progressive beta cell failure in diabetes.
Publication Title
Tungstate promotes β-cell survival in Irs2-/- mice.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Jarid2, a member of the Jumanji family of proteins, is a developmental regulator that is necessary for proper mouse development and stem cell differentiation. To investigate the specific functions of Jarid2 during pancreas development, we generated pancreas-specific Jarid2 mutants.
Publication Title
Late-stage differentiation of embryonic pancreatic β-cells requires Jarid2.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
AIMS/HYPOTHESIS: Manoeuvres aimed at increasing beta cell mass have been proposed as regenerative medicine strategies for diabetes treatment. Raf-1 kinase inhibitor protein 1 (RKIP1) is a common regulatory node of the mitogen-activated protein kinase (MAPK) and nuclear factor B (NF-B) pathways and therefore may be involved in regulation of beta cell homeostasis. The aim of this study was to investigate the involvement of RKIP1 in the control of beta cell mass and function.
Publication Title
The role of Raf-1 kinase inhibitor protein in the regulation of pancreatic beta cell proliferation in mice.
Sample Metadata Fields
Age, Specimen part
View Samples- Rattus norvegicus
- 15 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative analysis reveals novel pathways mediating the interaction between adipose tissue and pancreatic islets in obesity in rats.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Changes in the secretion profile of visceral-pancreatic white adipose tissue due to diet-induced obesity are partially responsible for increased beta cell replication, suggesting that a crosstalk between pWAT and beta cells may play a role in regulating beta cell plasticity. The molecular mechanisms underlying this cross-talk are still not fully understood.
Publication Title
Integrative analysis reveals novel pathways mediating the interaction between adipose tissue and pancreatic islets in obesity in rats.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 17 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
This experiment was designed to identify genes expressed preferentially in the two integuments of the Arabidopsis ovule. Pistils from wild type and two ovule mutants were compared against each aintegumenta-4 (ant-4) which lacks both integuments and inner no outer (ino-1) which lacks the outer integument. Genes that are highly expressed only in the integuments were expected to be reduced in expression in the mutants, as compared with wild type. Pistils containing ovules through all stages of ovule development prior to pollination were pooled for one experiment (FULL arrays), and for two separate experiments, a set of early differentiation stages (EARLY arrays) and a set of later differentiation stages (LATE ARRAYS) were pooled. Wild type and mutant lines are in the ecotype Landsberg erecta.
Publication Title
Expression-based discovery of candidate ovule development regulators through transcriptional profiling of ovule mutants.
Sample Metadata Fields
Specimen part
View Samples
SRP035359- Caenorhabditis elegans
- 77 Downloadable Samples
Illumina Genome Analyzer IIx
Description
We used RNA-Seq to compare transcriptomes of chemical reprogramming competent worms versus worms not competent for chemical reprogramming. We also performed RNA-seq during a time course of chemical reprogramming. Overall design: Three replicates of each of two reprogramming non-competent strains and three replicates of each of two reprogramming competent strains were collected. For the time course, five time points were analyzed (1, 2, 4, 6, and 18 hours) in either DMSO or DMSO + U0126 in three genotypes (non-reprogramming competent worms, reprogramming competent, and wildtype worms).
Publication Title
Competence for chemical reprogramming of sexual fate correlates with an intersexual molecular signature in Caenorhabditis elegans.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina HiSeq 2500
Description
The goal of this study is to compare gene expression profiles in quiescent RPE1 hTert cells treated with microtubule-stabilizing (paclitaxel) and microtubule-destabilizing poisons (combretastatin A4) Overall design: RPE 1 hTert cells were grown to full confluency, and maintained as such for 5 days to induce quiescence. Quiescent cells were treated with microtubule poisons combretastatin A4 and paclitaxel for 6 or 24 hours. Total RNA was collected and purified using the PureLink RNA Mini Kit (Invitrogen, Thermo Fisher Scientific, USA). RNA concentration and quality were determined using NanoDrop and Bioanalyzer respectively, and 500 ng of purified RNA was used as input for the Illumina TruSeq Stranded mRNA Library Prep Kit (Illumina, USA). Barcoded libraries were pooled and quantitated using KAPA, and single-end sequenced on an Illumina NextSeq (Illumina, USA). RNA-seq reads were mapped using STAR (version 2.1.0j) and processed using HTSeq-count (version 0.6.1). GRCh38 reference genome and transcript annotations were used for gene mapping; Entrez Gene identifiers and org.Hs.eg.db database were used for genome wide annotation. Differential gene expression and statistical analysis were performed using edgeR package. Genes with >50 reads per million and a fold change significantly different from zero in Wilcoxon signed-rank test (p< 0.05), were marked as differentially expressed genes, based on three biological replicates.
Publication Title
Tubulin mRNA stability is sensitive to change in microtubule dynamics caused by multiple physiological and toxic cues.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Microarray expression profiling has become a valuable tool in the evaluation of the genetic consequences of metabolic disease. Although 3-biased gene expression microarray platforms were the first generation to have widespread availability, newer platforms are gradually emerging that have more up-to-date content and/or higher cost efficiency. Deciphering the relative strengths and weaknesses of these various platforms for metabolic pathway level analyses can be daunting. We sought to determine the practical strengths and weaknesses of four leading commercially-available expression array platforms relative to biologic investigations, as well as assess the feasibility of cross-platform data integration for purposes of biochemical pathway analyses. METHODS: Liver RNA from B6.Alb/cre,Pdss2loxP/loxP mice having primary Coenzyme Q deficiency was extracted either at baseline or following treatment with an antioxidant/antihyperlipidemic agent, probucol. Target RNA samples were prepared and hybridized to Affymetrix 430 2.0, Affymetrix Gene 1.0 ST, Affymetrix Exon 1.0 ST, and Illumina Mouse WG-6 expression arrays. Probes on all platforms were re-mapped to coding sequences in the current version of the mouse genome. Data processing and statistical analysis were performed by R/Bioconductor functions, and pathway analyses were carried out by KEGG Atlas and GSEA. RESULTS: Expression measurements were generally consistent across platforms. However, intensive probe-level comparison suggested that differences in probe locations were a major source of inter-platform variance. In addition, genes expressed at low or intermediate levels had lower inter-platform reproducibility than highly expressed genes. All platforms showed similar patterns of differential expression between sample groups, with steroid biosynthesis consistently identified as the most down-regulated metabolic pathway by probucol treatment. CONCLUSIONS: This work offers a timely guide for metabolic disease investigators to enable informed end-user decisions regarding choice of expression microarray platform best-suited to specific research project goals. Successful cross-platform integration of biochemical pathway expression data is also demonstrated, especially for well-annotated and highly-expressed genes. However, integration of gene-level expression data is limited by individual platform probe design and the expression level of target genes. Cross-platform analyses of biochemical pathway data will require additional data processing and novel computational bioinformatics tools to address unique statistical challenges.
Publication Title
Cross-platform expression microarray performance in a mouse model of mitochondrial disease therapy.
Sample Metadata Fields
Sex, Age, Specimen part, Treatment
View Samples