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GSE11343
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- Homo sapiens
- 40 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Alternative processing of pre-mRNA transcripts is a major source of protein diversity in eukaryotes and has been implicated in several disease processes including cancer. In this study we have performed a genome wide analysis of alternative splicing events with the GeneChip Human Exon 1.0 ST Array from Affymetrix in lung adenocarcinoma. We found that ~13.3% of the 17800 core Refseq genes appear to have alternative transcripts that are differentially expressed in lung adenocarcinoma versus normal. According to their known functions the largest subset of these genes (30.8%) is believed to be cancer related. Detailed analysis was performed for several genes using PCR, quantitative RT-PCR and DNA sequencing. We found overexpression of ERG variant 2 but not variant 1 in lung tumors and overexpression of CEACAM1 variant 1 but not variant 2 in lung tumors but not in breast or colon tumors. We also identified a novel, overexpressed variant of CDH3 and verified the overexpression of a novel variant of P16. These findings demonstrate how analysis of alternative pre-mRNA processing can shed additional light on differences between tumors and normal tissues as well as between different tumor types. Such studies may lead to the development of additional tools for tumor diagnosis, prognosis and therapy.
Publication Title
Whole genome exon arrays identify differential expression of alternatively spliced, cancer-related genes in lung cancer.
Sample Metadata Fields
Sex, Age, Race, Subject
View Samples- Mus musculus
- 89 Downloadable Samples
Illumina HiSeq 2000
Description
Treating insulin resistance with pioglitazone normalizes renal function and improves small nerve fibre function and architecture; however, it does not affect large myelinated nerve fibre function in mouse models of type 2 diabetes (T2DM), indicating that pioglitazone affects the body in a tissue-specific manner. To identify distinct molecular pathways regulating diabetic peripheral neuropathy (DPN) and nephropathy (DN), as well those affected by pioglitazone, we assessed DPN and DN gene transcript expression in control and diabetic mice with or without pioglitazone treatment. Differential expression analysis and self-organizing maps were then used in parallel to analyse transcriptome data. Differential expression analysis showed that gene expression promoting cell death and the inflammatory response was reversed in the kidney glomeruli but unchanged or exacerbated in sciatic nerve by pioglitazone. Self-organizing map analysis revealed that mitochondrial dysfunction was normalized in kidney and nerve by treatment; however, conserved pathways were opposite in their directionality of regulation. Collectively, our data suggest inflammation may drive large fibre dysfunction, while mitochondrial dysfunction may drive small fibre dysfunction in T2DM. Moreover, targeting both of these pathways is likely to improve DN. This study supports growing evidence that systemic metabolic changes in T2DM are associated with distinct tissue-specific metabolic reprogramming in kidney and nerve and that these changes play a critical role in DN and small fibre DPN pathogenesis. These data also highlight the potential dangers of a 'one size fits all' approach to T2DM therapeutics, as the same drug may simultaneously alleviate one complication while exacerbating another. PMID: 28272773 Overall design: mRNA profiles of four diabetic complication-prone tissues (sciatic nerve, dorsal root ganglia, kidney glomeruli and kidney cortex) from 16-week old BKS.Cg-m +/+ Leprdb/J mice with/without pioglitazone treatment of 15 mg/kg for 11 weeks. db/db genetic model was used for type 2 diabetes model. Deep sequencing of six biological replicates in each tissues using Illumina HiSeq 2000.
Publication Title
Comparative RNA-Seq transcriptome analyses reveal distinct metabolic pathways in diabetic nerve and kidney disease.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
We studied whether the accumulation of lipids in the fasted kidney are derived from lipoproteins or (non-esterified fatty acids) NEFAs. With overnight fasting, kidneys accumulated triglyceride, but had reduced levels of ceramide and glycosphingolipid species. Fasting led to a nearly 5-fold increase in kidney uptake of plasma [14C]oleic acid. Increasing circulating NEFAs using a ß adrenergic receptor agonist caused a 15-fold greater accumulation of lipid in the kidney, while mice with reduced NEFAs due to adipose tissue deficiency of adipose triglyceride lipase had reduced triglycerides. Cluster of differentiation (Cd)36 mRNA increased 2-fold, and angiopoietin-like 4 (Angptl4), an LPL inhibitor, increased 10-fold. Fasting-induced kidney lipid accumulation was not affected by inhibition of LPL with poloxamer 407 or by use of mice with induced genetic LPL deletion. Despite the increase in CD36 expression with fasting, genetic loss of CD36 did not alter fatty acid uptake or triglyceride accumulation. Our data demonstrate that fasting-induced triglyceride accumulation in the kidney correlates with the plasma concentrations of NEFAs, but is not due to uptake of lipoprotein lipids and does not involve the fatty acid transporter, CD36. Overall design: Mice (n=4-5/group) were either fasted for 16 hours or fed ad libitum. Kidneys were removed and snap frozen. RNA was extracted for sequencing.
Publication Title
Kidney triglyceride accumulation in the fasted mouse is dependent upon serum free fatty acids.
Sample Metadata Fields
Sex, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 90 Downloadable Samples
- Affymetrix HT HG-U133+ PM Array Plate (hthgu133pluspm)
Description
Here we studied the effects of anticonvulsant drug exposure in a human embryonic stem cell (hESC) based neuro- developmental toxicity test (hESTn). During neural differentiation the cells were exposed, for either 1 or 7 days, to non-cytotoxic concentration ranges of valproic acid (VPA) or carbamazepine (CBZ), anti-epileptic drugs known to cause neurodevelopmental toxicity.
Publication Title
Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 90 Downloadable Samples
- NextSeq 500
Description
Regulatory T cells (T regs) maintain host self-tolerance but are a major barrier to effective cancer immunotherapy. T regs subvert beneficial anti-tumor immunity by modulating inhibitory receptor (IR) expression on tumor infiltrating lymphocytes (TILs); however, the underlying mediators and mechanisms remain elusive. Here we show that interleukin-10 (IL10) and interleukin-35 (IL35; Ebi3/IL12a heterodimer) are divergently expressed by T reg subpopulations in the tumor microenvironment (TME) and cooperatively promote intratumoral T cell exhaustion. T reg -restricted deletion of Il10 and/or Ebi3 resulted in delayed tumor growth, loss of multi-IR expression, and reduced intratumoral CD8 + T cell exhaustion signature. While Il10 or Ebi3 loss was associated with reduced expression of B lymphocyte-induced maturation protein-1 (BLIMP1; Prdm1), IL10 and IL35 differentially impacted effector versus memory T cell fates, respectively, highlighting their differential, partially overlapping but non-redundant regulation of anti-tumor immunity. Our results reveal previously unappreciated cooperative roles for IL10 and IL35, produced by limits effective anti-tumor immunity Overall design: TIL CD8 cells from Treg specific IL10, IL35 and double knockouts, sorted into populations based on exhaustion markers. TIL Tregs sorted based on IL10 and IL35 expression.
Publication Title
Adaptive plasticity of IL-10<sup>+</sup> and IL-35<sup>+</sup> T<sub>reg</sub> cells cooperatively promotes tumor T cell exhaustion.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- NextSeq 500
Description
Abstract: Regulatory T cells (Tregs) maintain host self-tolerance but are a major barrier to effective cancer immunotherapy. Tregs subvert beneficial anti-tumor immunity by modulating inhibitory receptor (IR) expression on tumor infiltrating lymphocytes (TILs); however, the underlying mediators and mechanisms remain elusive. Here we show that interleukin-10 (IL10) and interleukin-35 (IL35; a heterodimer of Ebi3 and IL12?) are reciprocally expressed by Treg-subpopulations in the tumor microenvironment (TME) and cooperatively promote intratumoral T cell exhaustion. Treg-restricted deletion of either Il10/Ebi3 or dual deletion resulted in delayed tumor growth and significant reduction of transcriptomic exhaustion signature associated with reduced expression of B lymphocyte-induced maturation protein-1 (BLIMP1; Prdm1). While the two cytokines share the BLIMP1 axis to drive multi-IR expression; they differentially impact effector vs. memory fate, highlighting their overlapping and non-redundant regulation of anti-tumor immunity. Our results reveal previously unappreciated adaptive plasticity in inhibitory cytokine expression pattern by Tregs in TME for maximal immunosuppression. Data purpose: to understand the segregated cytokine expression pattern and the preferential generation of single cytokine positive Treg subpopulations, we performed single cell RNASeq (scRNAseq) contrasting Tregs isolated from naïve, unchallenged LNs or day 14 B16 tumor from Foxp3Cre-YFP WT mice Overall design: LNs or day 14 B16 tumor from Foxp3Cre-YFP WT mice
Publication Title
Adaptive plasticity of IL-10<sup>+</sup> and IL-35<sup>+</sup> T<sub>reg</sub> cells cooperatively promotes tumor T cell exhaustion.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Danio rerio
- 188 Downloadable Samples
- Affymetrix Genechip Zebrafish ST Genome Array 1.1 (zebgene11st)
Description
Zebrafish embryos have been proposed as an attractive alternative model system for hepatotoxicity testing.
Publication Title
A transcriptomics-based hepatotoxicity comparison between the zebrafish embryo and established human and rodent in vitro and in vivo models using cyclosporine A, amiodarone and acetaminophen.
Sample Metadata Fields
Compound
View Samples- Homo sapiens
- 188 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We performed gene expression profiling of laser capture microdissected normal non-neoplastic prostate (cystoprostatectomies) epithelial tissue and compared it to non-transformed and neoplastic low and high grade prostate epithelial tissue from radical prostatectomies, each with its immediately surrounding stroma.
Publication Title
Stromal and epithelial transcriptional map of initiation progression and metastatic potential of human prostate cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
In acute promyelocytic leukemia (APL), differentiation therapy with all-trans retinoic acid (ATRA)
Publication Title
Chemokine induction by all-trans retinoic acid and arsenic trioxide in acute promyelocytic leukemia: triggering the differentiation syndrome.
Sample Metadata Fields
Specimen part
View Samples