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GSE95298
Homo sapiens
55 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Most FDA approved drugs are not equally effective in all patients, suggesting that identification of biomarkers to predict responders to a chemoprevention agent will be needed to stratify patients and achieve maximum benefit. The goal of this study was to investigate both patient specific and cell-context specific heterogeneity of metformin response, using cancer cell lines fibroblast cell lines and induced pluripotent stem cells differentiated into lung epithelial lineages.
Publication Title
Patient- and Cell Type-Specific Heterogeneity of Metformin Response.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 14 Downloadable Samples
Illumina HiSeq 2000
Description
Through the generation of humanized FUS mice expressing full length human FUS, we identify that when expressed at near endogenous murine FUS levels both wild-type or ALS- and frontotemporal dementia (FTD)-causing mutations complement the essential function(s) of murine FUS. Replacement of murine FUS with mutant, but not wild-type, human FUS causes stress-mediated induction of chaperones, decreased expression of ion channels/transporters essential for synaptic function, and reduced synaptic activity, without loss of nuclear FUS or its cytoplasmic aggregation. Most strikingly, accumulation of mutant human FUS is shown to activate an integrated stress response and inhibit local, intra-axonal protein synthesis in hippocampal neurons and sciatic nerves. Collectively, our evidence demonstrates that human ALS/FTD-linked mutations in FUS induce a gain-of-toxicity that includes stress-mediated suppression in intra-axonal translation, synaptic dysfunction, and progressive, age-dependent motor and cognitive disease without cytoplasmic aggregation, altered nuclear localization, or aberrant splicing of FUS-bound pre-mRNAs. Methods: RNA from mouse spinal cords of 18-month-old mFUS-/-/hgFUS (WT, R521C or R521H) and their Non-Tg control littermates was extracted with TRIzol. RNA quality was measured using the Agilent Bioanalyzer system and processed using the Illumina TruSeq Stranded mRNA Sample Preparation Kit according to manufacturer's protocols. mRNA profiles were generated by deep sequencing, with n=3 biological replicates per group. Results: We mapped on average 15 million non-redundant reads per sample. Fastq files were aligned to mouse reference genome (mm9 UCSC Genome Browser) using TopHat workfow and the transcript abundance for each annotated protein-coding gene [as fragments per kilobase of transcript per million mapped reads (FPKM)] was estimated by Cufflinks. 13,468 genes which expressed FPKM>=1 were kept for downstream analyses. RNA profiles from normal (Non-Tg) and humanized hgFUSWT mice were almost undistinguishable. Both humanized mutant FUS lines had highly distinct RNA profiles [determined with unsupervised hierarchical clustering and principal component analysis (PCA)], with 709 down and 348 up-regulated genes relative to age-matched Non-Tg or humanized hgFUSWT littermates (P<0.05). These changes uncovered FUS mutant dependent altered pathways that may contribute to ALS/FTD-linked mutant FUS-mediated toxicity. The validation by RT-QPCR of altered expression of 20 genes is shown in Figure 5. Overall design: RNA expression profile of mouse spinal cords from 18-month-old mFUS-/-/hgFUS (WT, R521C or R521H) and their Non-Tg control littermates was obtained by deep sequencing in n=3 indendepent animals per genotype using Illumina HiSeq 2000 sequencer.
Publication Title
ALS/FTD-Linked Mutation in FUS Suppresses Intra-axonal Protein Synthesis and Drives Disease Without Nuclear Loss-of-Function of FUS.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Epithelial tumor cells (E) underwent EMT in vivo in FVB/N mice generating mesenchymal tumors. Mesenchymal cell lines (M1-M4) were each derived from a different mouse. This study compares gene expression between these two different tumor types.
Publication Title
Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Caenorhabditis elegans
- 8 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
RRF-3 and ERI-1 are first identified proteins required for accumulation of at least some endogenous secondary siRNAs in C.elegans. Genome wide gene expression analysis was performed on L4 stage rrf-3 and eri-1 mutant C. elegans to study effects caused by loss of these proteins. Mutant rrf-3 and eri-1 strains exhibited similar expression patterns when compared to N2 wild type, while 72 transcripts were found to be co-overexpressed and 4 transcripts co-underexpressed (> 2-fold, p< 0.05). Ontology analysis indicated many of the gene products were associated with protein phosphorylation and sperm function. These results provide additional support for the hypothesis that RRF-3 and ERI-1 act together in a siRNA pathway and may indicate biological processes that are related to endo-siRNAs.
Publication Title
Whole genome microarray analysis of C. elegans rrf-3 and eri-1 mutants.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Ob/ob mice were given 0, 12.5 or 25 ng/hr leptin through an osmotic pump. After 12 days, livers RNA was prepared and illumina microarrays were done. We tested whether leptin can ameliorate diabetes independent of weight loss by defining the lowest dose at which leptin treatment of ob/ob mice reduces plasma [glucose] and [insulin]. We found that a leptin dose of 12.5 ng/hour significantly lowers blood glucose and that 25 ng/hour of leptin normalizes plasma glucose and insulin without significantly reducing body weight, thus establishing that leptin exerts its most potent effects on glucose metabolism. To find possible mediators of this effect, we profiled liver mRNA using microarrays and identified IGF Binding Protein 2 as being regulated by leptin with a similarly high potency. Over-expression of IGFBP2 by an adenovirus reversed diabetes in insulin resistant ob/ob, Ay/a and diet-induced obese mice (DIO), as well as insulin deficient streptozotocin-treated mice. Hyperinsulinemic clamp studies showed a three-fold improvement in hepatic insulin sensitivity following IGFBP2 treatment in ob/ob mice. These results show that IGFBP2 can regulate glucose metabolism, a finding with potential implications for the pathogenesis and treatment of diabetes.
Publication Title
Antidiabetic effects of IGFBP2, a leptin-regulated gene.
Sample Metadata Fields
Specimen part, Time
View Samples- Gossypium hirsutum
- 89 Downloadable Samples
- Affymetrix Cotton Genome Array (cotton)
Description
Cotton fiber were used for the expression analysis at different developmental stages
Publication Title
Transcriptome dynamics during fibre development in contrasting genotypes of Gossypium hirsutum L.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 332 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Network pharmacology of JAK inhibitors.
Sample Metadata Fields
Sex, Age, Specimen part, Compound
View Samples- Mus musculus
- 238 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Small molecule inhibitors of JAK kinases have shown clinical effcacy in the treatment of certain autoimmune diseases. While these are known to block upstream JAK signalling events, their broader impact on the transcriptional footprint in immunocytes are unknown. Here we explore the effects of pan- and isoform-specific JAK blockade on the immuno-genomic network by genomic profiling.
Publication Title
Network pharmacology of JAK inhibitors.
Sample Metadata Fields
Sex, Age, Specimen part, Compound
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
B cells respond robustly to type 1 interferons which signal through JAK1 and TYK2. Here we analyzed the effects of a panel of JAK inhibitors on the IFNa transcriptional response in activated B cells in vitro.
Publication Title
Network pharmacology of JAK inhibitors.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
IL2 signals are transmitted through JAK1 and JAK3, but the transcriptomic consequences of each to the overall response is unclear. Here we analyzed the relative contribution of JAK1 and JAK3 to the NK cell IL2 response in vitro using titrated doses of isoform specific JAK inhibitors. Blockade of JAK1 and JAK3 have unequal effects on IL2-induced transcripts at pharmacologically relevant doses.
Publication Title
Network pharmacology of JAK inhibitors.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples