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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- Homo sapiens
- 45 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Hypoxia may cause pulmonary and brain edema, pulmonary hypertension, aberrant metabolism and early mortality. To better understand pathological processes associated with hypoxia, we examined gene expression in Chuvash polycythemia (CP) blood mononuclear cells. CP is a congenital disorder of up-regulated hypoxic response at normoxia wherein VHLR200W homozygosity leads to elevated hypoxia inducible factor (HIF)-1 and HIF-2 levels, thromboses, pulmonary hypertension, lower systemic blood pressure (SBP) and increased mortality. VHLR200W homozygotes are often treated by phlebotomy resulting in iron deficiency, allowing us to evaluate an interaction of augmented hypoxia sensing with iron deficiency.
Publication Title
Iron deficiency modifies gene expression variation induced by augmented hypoxia sensing.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The transcription factor IRF4 regulates immunoglobulin class switch recombination and plasma cell differentiation. Its differing concentrations appear to regulate mutually antagonistic programs of B and plasma cell gene expression. We show IRF4 to be also required for generation of germinal center (GC) B cells. Its transient expression in vivo induced the expression of key GC genes including Bcl6 and Aicda. In contrast, sustained and higher concentrations of IRF4 promoted the generation of plasma cells while antagonizing the GC fate. IRF4 cobound with the transcription factors PU.1 or BATF to Ets or AP-1 composite motifs, associated with genes involved in B cell activation and the GC response. At higher concentrations, IRF4 binding shifted to interferon sequence response motifs; these enriched for genes involved in plasma cell differentiation. Our results support a model of "kinetic control" in which signaling-induced dynamics of IRF4 in activated B cells control their cell-fate outcomes.
Publication Title
Transcriptional regulation of germinal center B and plasma cell fates by dynamical control of IRF4.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Temporal analysis of B cell activation in vitro using CD40L and IL-2/4/5 cytokines in wild type Irf4+/+ B cells or in mutant Irf4-/- B cells harboring a tet-inducible allele of Irf4. IRF4 expression was restored, or not, in the Irf4-/- background by culturing in the presence of low or high concentrations of doxycycline. The results provide insight in the role of IRF4 expression levels in coordinating different programs of B cell differentiation.
Publication Title
Transcriptional regulation of germinal center B and plasma cell fates by dynamical control of IRF4.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 26 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
African American men are disproportionately affected by both vitamin D deficiency and increased risk of prostate cancer.
Publication Title
Prostatic compensation of the vitamin D axis in African American men.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Illumina MouseRef-8 v2.0 expression beadchip
Description
Using the stringent criteria (fold change 1.5 up or down, P < 0.01, FDR < 0.05) to filter significantly differentially expressed genes, we did not identify any genes whose expression levels were significantly different between the PBS and PBS+LZD groups or between the LAC and LAC+LZD at Day 1 or Day 3 post MRSA infection. However, a remarkable difference was demonstrated (Figure 5A) between PBS and LAC groups at either Day 1 or Day 3 post MRSA infection.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part, Treatment, Time
View Samples- Homo sapiens
- 6 Downloadable Samples
Affymetrix Human Gene Expression Array (primeview), Illumina HiSeq 2000
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Nitric Oxide Regulates Gene Expression in Cancers by Controlling Histone Posttranslational Modifications.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Global gene expression profiling is useful for elucidating a drug?s mechanism of action (MOA) on the liver; however, such profiling in rats is not very sensitive for predicting human druginduced liver injury, while de-differentiated monolayers of primary human hepatocytes (PHHs) do not permit chronic drug treatment. In contrast, micropatterned co-cultures (MPCCs) containing PHH colonies and 3T3-J2 fibroblasts maintain a stable liver phenotype for 4-6 weeks. Here, we used MPCCs to test the hypothesis that global gene expression patterns in stable PHHs can be used to distinguish clinical hepatotoxic drugs from their non-liver-toxic analogs and understand the MOA prior to the onset of overt hepatotoxicity. We found that MPCCs treated with the clinical hepatotoxic/non-liver-toxic pair, troglitazone/rosiglitazone, at each drug?s reported and non-toxic Cmax (maximum concentration in human plasma) level for 1, 7, and 14 days displayed a total of 12, 269, and 628 differentially expressed genes, respectively, relative to the vehicle-treated control. Troglitazone modulated >75% of transcripts across pathways such as fatty acid and drug metabolism, oxidative stress, inflammatory response, and complement/coagulation cascades. Escalating rosiglitazone?s dose to that of troglitazone?s Cmax increased modulated transcripts relative to the lower dose; however, over half the identified transcripts were still exclusively modulated by troglitazone. Lastly, other hepatotoxins (nefazodone, ibufenac, and tolcapone) also induced a greater number of differentially expressed genes in MPCCs than their non-liver-toxic analogs (buspirone, ibuprofen, and entacapone) following 7 days of treatment. In conclusion, MPCCs allow evaluation of time- and dose-dependent gene expression patterns in PHHs treated chronically with analog drugs.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Treatment
View Samples- Drosophila melanogaster
- 17 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Apoptosis is an important process to eliminate cells from tissue which have incurred irreparable DNA damage. While dE2F1/dDP complexes respond to such damage by transcriptionally activating apoptotic genes, previous data suggests that activation of the previously characterized apoptotic target genes of dE2F1/dDP alone may not be the only gene regulation important for gamma irradiation-induced apoptosis. Here we report that following irradiation in dDP mutant 3rd instar larval eye imaginal discs, many genes important for oxidative phosphorylation are down-regulated, which are not down-regulated following irradiation in wild type eye discs.
Publication Title
Loss of dE2F compromises mitochondrial function.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 13 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Organotypic in vitro culture is useful to model mammalian disease in numerous tissues. Normal epithelial differentiation and carcinogenesis both undergo in vivo regulation by stroma, but current culture methods exclude stroma. To mimic this in vivo environment, we developed and characterized a human 3D prostate organoid co-culture model that incorporates prostate stroma. Primary prostate stromal cells supported increased organoid formation and expressed growth factors and WNT-related genes involved in epithelial differentiation. Organoid branching occurred distal to physical contact with stromal cells, demonstrating non-random branching. Tumoroids derived from primary prostate cancer maintained differential expression of the prostate cancer marker AMACR only in the presence of stroma. Stroma-induced phenotypes were similar in all patients examined, yet maintained inter-patient heterogeneity in the degree of response. Addition of stroma to in vitro organoid culture recapitulated the in vivo microenvironment by inducing organization of benign organoids into branching structures and preserving prostate cancer phenotypes.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples