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Homo sapiens
6 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Increased ploidy is common in tumors but treatments for tumors with excess chromosome sets are not available. Here, we characterize high-ploidy breast cancers and identify potential anticancer compounds selective for the high-ploidy state. Among 354 human breast cancers, 10% have mean chromosome copy number exceeding 3, and this is most common in triple negative and HER2-positive types. Women with high-ploidy breast cancers have higher risk of recurrence and death in two patient cohorts, demonstrating that it represents an important group for improved treatment. Because high-ploidy cancers are aneuploid, rather than triploid or tetraploid, we devised a two-step screen to identify selective compounds. The screen was designed to assure both external validity on diverse karyotypic backgrounds and specificity for high-ploidy cell types. This screen identified novel therapies specific to high-ploidy cells. First, we discovered 8-azaguanine, an antimetabolite that is activated by hypoxanthine phosphoribosyltransferase (HPRT), suggesting an elevated gene-dosage of HPRT in high-ploidy tumors can control sensitivity to this drug. Second, we discovered a novel compound, 2,3-Diphenylbenzo[g]quinoxaline-5,10-dione (DPBQ). DPBQ activates p53 and triggers apoptosis in a polyploid-specific manner, but does not inhibit topoisomerase or bind DNA. Mechanistic analysis demonstrates that DPBQ elicits a hypoxia gene signature and its effect is replicated, in part, by enhancing oxidative stress. Structure-function analysis defines the core benzo[g]quinoxaline-5,10 dione as being necessary for the polyploid-specific effects of DPBQ. We conclude that polyploid breast cancers represent a high-risk subgroup and that DPBQ provides a functional core to develop polyploid-selective therapy.
Publication Title
Identification of Selective Lead Compounds for Treatment of High-Ploidy Breast Cancer.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
To analyze the role of DNA methylation during differentiation, we performed genome-wide expression analysis of undifferentiated wild type, dnmt1-/- and triple knock out (TKO; dnmt1-/-, dnmt3a-/-, dnmt3b-/-) ESCs as well as respective embryoid bodies (EBs) at two stages of differentiation
Publication Title
Global DNA hypomethylation prevents consolidation of differentiation programs and allows reversion to the embryonic stem cell state.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
TCP transcription factors from the CYC2-class are involved in the development of monosymmetric flowers in all core eudicot species analysed so far. In Antirrhinum majus, the CYC2/TCP transcription factor CYCLOIDEA (CYC) is the molecular key regulator driving the development of flower monosymmetry (Luo D, Carpenter R, Vincent C, Copsey L, Coen E: Origin of floral asymmetry in Antirrhinum. Nature 1996, 383:794-799). In the Brassicaceae Iberis amara, a stronger expression of the CYC2 gene IaTCP1 in the small adaxial petals likely leads to the reduced petal size in comparison to large abaxial petals, with hardly any IaTCP1 expression. This results in the formation of the monosymmetric Iberis flower (Busch A, Zachgo S: Control of corolla monosymmetry in the Brassicaceae Iberis amara. PNAS 2007, 104:16714-16719). In contrast, the orthologous TCP/CYC2 transcription factor TCP1 from Arabidopsis thaliana, which forms equally sized and shaped petal pairs, only shows an early and transient expression in the adaxial area of floral primordia. This implies that monosymmetry in the Brassicaceae evolved through a heterochronic expression shift of the TCP/CYC2 key regulator gene IaTCP1.
Publication Title
Differential transcriptome analysis reveals insight into monosymmetric corolla development of the crucifer Iberis amara.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Over activation of the aryl hydrocarbon receptor (AhR) by TCDD results ampng other phenotypes in severe thymic atrophy accompanied by immunosuppression. The link between thymic atrophy, skewed thymocyte differntiation and immunosuppression is still not fully resolved. This study investigates the TCDD elicted exprssion changes in the ET, cortical thymus epithelial cell line.
Publication Title
Promoter analysis of TCDD-inducible genes in a thymic epithelial cell line indicates the potential for cell-specific transcription factor crosstalk in the AhR response.
Sample Metadata Fields
Treatment, Time
View Samples
GSE1919- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Genome U95A Array (hgu95a)
Description
Rheumatoid arthritis (RA) is a chronic, inflammatory joint disease of unknown etiology and pronounced inter-patient heterogeneity. To characterize RA at the molecular level and to uncover key pathomechanisms, we performed whole-genome gene expression analyses. Synovial tissues from rheumatoid arthritis patients were compared to those from osteoarthritis patients and to normal donors.
Publication Title
Molecular signatures and new candidates to target the pathogenesis of rheumatoid arthritis.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 54 Downloadable Samples
Illumina HiSeq 2500
Description
Dose-dependent femoral gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure on gene expression in the femur of C57BL/6 male mice. Overall design: Three biological replicates for each dose (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30) of TCDD and sesame oil vehicle
Publication Title
2,3,7,8-Tetrachlorodibenzo-p-dioxin dose-dependently increases bone mass and decreases marrow adiposity in juvenile mice.
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Microarray data from G2-synchronized p53(+) and p53(-) fibroblasts before and after 3 h release from cell cycle blockade in the presence of 5 M sodium arsenite.
Publication Title
Exit from arsenite-induced mitotic arrest is p53 dependent.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
During organogenesis of the intestine, reciprocal crosstalk between the endodermally-derived epithelium and the underlying mesenchyme is required for regional patterning and proper differentiation. Though both of these tissue layers participate in patterning, the mesenchyme is thought to play a prominant role in the determination of epithelial phenotype during development and in adult life. However, the molecular basis of this instructional dominance is unclear. In fact, surprisingly little is known about the cellular origins of many of the critical signaling molecules and the gene transcriptional events that they impact. Here, we profile genes that are expressed in separated mesenchymal and epithelial compartments of the perinatal mouse intestine. The data indicate that the vast majority of soluble modulators of signaling pathways such as Hedgehog, Bmp, Wnt, Fgf and Igf are expressed predominantly or exclusively by the mesenchyme, accounting for its ability to dominate instructional crosstalk. We also catalog the most highly enriched transcription factors in both compartments and find evidence for a major role for Hnf4alpha and Hnf4 gamma in the regulation of epithelial genes. Finally, we find that while epithelially enriched genes tend to be highly tissue-restricted in their expression, mesenchymally-enriched genes tend to be broadly expressed in multiple tissues. Thus, the unique tissue-specific signature that characterizes the intestinal epithelium is instructed and supported by a mesenchyme that itself expresses genes that are largely non-tissue specific.
Publication Title
Deconvoluting the intestine: molecular evidence for a major role of the mesenchyme in the modulation of signaling cross talk.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 54 Downloadable Samples
- Illumina HiSeq 2500
Description
Dose-dependent ileal gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure on gene expression in the intestinal epithelium of C57BL/6 male mice. Overall design: Three biological replicates for each dose (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30) of TCDD and sesame oil vehicle
Publication Title
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-elicited effects on bile acid homeostasis: Alterations in biosynthesis, enterohepatic circulation, and microbial metabolism.
Sample Metadata Fields
Sex, Cell line, Treatment, Subject
View Samples- Mus musculus
- 54 Downloadable Samples
- Illumina HiSeq 2500
Description
Dose-dependent duodenal gene expression was examined following repeated exposure (every 4 days for 28 days) to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). These data were used to examine the effect of repeated TCDD exposure on gene expression in the intestinal epithelium of C57BL/6 male mice. Overall design: Three biological replicates for each dose (0.01, 0.03, 0.1, 0.3, 1, 3, 10, 30) of TCDD and sesame oil vehicle
Publication Title
Convergence of hepcidin deficiency, systemic iron overloading, heme accumulation, and REV-ERBα/β activation in aryl hydrocarbon receptor-elicited hepatotoxicity.
Sample Metadata Fields
Sex, Specimen part, Cell line, Treatment, Subject
View Samples