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GSE146615
Homo sapiens
144 Downloadable Samples
Illumina HumanHT-12 V4.0 expression beadchip
Description
The goal of the study was to identify genes whose aberrant expression can contribute to diabetic retinopathy. We determined differential response in gene expression to high glucose in lymphoblastoid cell lines derived from matched type 1 diabetic individuals with and without retinopathy. Those genes exhibiting the largest difference in glucose response between diabetic subjects with and without retinopathy were assessed for association to diabetic retinopathy utilizing genotype data from a meta-genome-wide association study. All genetic variants associated with gene expression (expression QTLs; eQTLs) of the glucose response genes were tested for association with diabetic retinopathy. We detected an enrichment of the glucose response gene eQTLs among small association p-values for diabetic retinopathy. Among these, we identified FLCN as a susceptibility gene for diabetic retinopathy. Expression of FLCN in response to glucose is greater in individuals with diabetic retinopathy compared to diabetic individuals without retinopathy. Three large, independent cohorts of diabetic individuals revealed an enhanced association of FLCN eQTL to diabetic retinopathy. Mendelian randomization confirmed a direct positive effect of increased FLCN expression on retinopathy in diabetic individuals. Together, our studies integrating genetic association and gene expression implicate FLCN as a disease gene in diabetic retinopathy.
Publication Title
Integration of genomics and transcriptomics predicts diabetic retinopathy susceptibility genes.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 28 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We identified a congenic mouse with an introgressed region from the A/J donor inbred strain on an inbred C57BL/6J background that showed a reduced locomotor stimulant response to methamphetamine. We conducted microarray analysis of the striatum from drug-naive female and male mice that were 6-9 weeks old. The congenic region is on chromosome 11 and spans approximately 84-96 Mb. There were two groups of mice used in the analysis: B6 control mice versus congenic mice. Congenic mice were collapsed across heterozygous and homozygous genotypes.
Publication Title
Congenic dissection of a major QTL for methamphetamine sensitivity implicates epistasis.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 31 Downloadable Samples
Illumina HiSeq 2000
Description
Microcephaly and medulloblastoma result from mutations that compromise genomic stability. We report that Atr, which is mutated in the microcephalic disorder Seckel syndrome, is required to maintain chromosomal integrity during postnatal cerebellar neurogenesis. Atr deletion in cerebellar granule neuron progenitors (CGNPs) induced proliferation-associated DNA damage, p53 activation, apoptosis, and cerebellar hypoplasia. Co-deletions of either Bax and Bak or p53 prevented apoptosis in Atr-deleted CGNPs, but failed to fully rescue cerebellar growth. Atr-deficient CGNPs showed impaired cell cycle checkpoint function and continued to proliferate, accumulating chromosomal abnormalities. RNA-Seq demonstrated that the transcriptional response to Atr-deficient proliferation was p53-driven. Acute Atr inhibition in vivo by nanoparticle-formulated VE-822 reproduced the disruptions seen with Atr deletion. Our data show that p53-driven apoptosis and senescence, and non-apoptotic cell death redundantly limit growth in Atr-deficient progenitors. These overlapping mechanisms that suppress growth in Atr-disrupted CGNPs may be exploited for treatment of CGNP-derived medulloblastoma using Atr inhibition. Overall design: RNA-Seq on total RNA from P3 mouse cerebella of Math1-Cre;Atr-loxP/loxP;Bax-loxP/loxP;Bak--/- (n=5), Math1-Cre;Bax-loxP/loxP;Bak--/- (n=4), Math1-Cre;Atr-loxP/loxP;p53-loxP/loxP (n=5), and Math1-Cre;p53-loxP/loxP (n=3), all run in 2 lanes
Publication Title
ATR maintains chromosomal integrity during postnatal cerebellar neurogenesis and is required for medulloblastoma formation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HiSeq 2000
Description
The combination of JQ1 and Vemurafenib acted synergistically in BRAF-mutant cell lines, resulting in marked apoptosis in vitro, with up-regulation of pro-apoptotic proteins. In vivo, combination treatment suppressed tumor growth and significantly improved survival compared to either drug alone. RNA sequencing of tumor tissues revealed almost four thousand genes that were uniquely modulated by the combination, with several anti-apoptotic genes significantly down-regulated. Overall design: 16 samples analyzed from 8 mice (each mouse was bearing two tumors, one on each flank) in 4 treatment groups (control, vemurafenib alone, JQ1 alone, JQ1+vemurafenib)
Publication Title
BET and BRAF inhibitors act synergistically against BRAF-mutant melanoma.
Sample Metadata Fields
Cell line, Treatment, Subject
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Malignant carcinomas that recur following therapy are typically de-differentiated and multi-drug resistant (MDR). De-differentiated cancer cells acquire MDR by upregulating reactive oxygen species (ROS)-scavenging enzymes and drug efflux pumps, but how these genes are upregulated in response to de-differentiation is not known. Here, we examine this question by using global transcriptional profiling to identify ROS-induced genes that are already upregulated in de-differentiated cells, even in the absence of oxidative damage.
Publication Title
De-differentiation confers multidrug resistance via noncanonical PERK-Nrf2 signaling.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- Illumina HiSeq 2000
Description
Epidemiological studies provide strong evidence that consumption of cruciferous vegetables, such as broccoli, can significantly reduce the risk of developing cancers. Sulforaphane (SFN), a phytochemical derived from cruciferous vegetables, induces anti-proliferative and pro-apoptotic responses in prostate cancer cells, but not in normal prostate cells. The mechanisms responsible for these specific chemopreventive properties remain unclear. We utilized RNA sequencing to test the hypothesis that SFN modifies the expression of genes that are critical in prostate cancer progression. Normal prostate epithelial cells, and androgen-dependent and androgen-independent prostate cancer cells were treated with 15 µM SFN and the transcriptome was determined at 6 and 24 hour time points. SFN altered the expression of ~3,000 genes in each cell line and the response was highly dynamic over time. SFN influenced the expression of genes in functional groups and pathways that are critical in cancer including cell cycle, apoptosis and angiogenesis, but the specific effects of SFN differed depending on the state of cancer progression. Network analysis suggested that a transcription factor that is overexpressed in many cancers, Specificity protein 1 (Sp1), is a major mediator of SFN-induced changes in gene expression. Nuclear Sp1 protein was significantly decreased by 24 hour SFN treatment in prostate cancer cells, while a related transcription factor, Sp3 protein was only modestly decreased in androgen-independent prostate cancer cells. Overall, the data show that SFN significantly affects gene expression in normal and cancer cells, with key targets in chemopreventive processes, making it a promising dietary anti-cancer agent. Overall design: Examination of how the transcriptome of normal and prostate cancer cells is altered by treatment with sulforaphane
Publication Title
Transcriptome analysis reveals a dynamic and differential transcriptional response to sulforaphane in normal and prostate cancer cells and suggests a role for Sp1 in chemoprevention.
Sample Metadata Fields
Specimen part, Subject, Time
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st), Illumina Genome Analyzer IIx
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide screen of cell-cycle regulators in normal and tumor cells identifies a differential response to nucleosome depletion.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 32 Downloadable Samples
- Illumina Genome Analyzer IIx, Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Gene-expression in siRNA treated U2OS and hTERT-RPE1 cells showed that CASP8AP2, NPAT and HINFP do not regulate expression of each other, and do not have any common target genes, except histones. Most histone genes are downregulated in U2OS cells following loss of CASP8AP2, NPAT or HINFP. In normal cells, highly-expressed histone genes were downregulated, albeit less than in tumor cells following loss of CASP8AP2. The p53 target genes were upregulated relatively late, clearly after the changes in expression of histone genes were observed.
Publication Title
Genome-wide screen of cell-cycle regulators in normal and tumor cells identifies a differential response to nucleosome depletion.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
We generated mice with a transgenic BAC on a B6 background. The BAC contains Glo1, and the transgenic mice were found to overexpress Glo1.
Publication Title
Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal.
Sample Metadata Fields
Sex, Specimen part
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- NextSeq 500
Description
we performed transcriptomic analysis of the RanBP9del1 mutant ovaries compared to wild type Overall design: explore the consequences of decreased nuclear actin on transcription
Publication Title
Nuclear Actin Is Required for Transcription during Drosophila Oogenesis.
Sample Metadata Fields
Subject
View Samples