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GSE39890
Homo sapiens
14 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Despite their distinct biology, granulosa cell tumours (GCTs) are treated the same as other ovarian tumours. Intriguingly, a recurring somatic mutation in the transcription factor Forkhead Box L2 (FOXL2) 402C>G has been found in nearly all GCTs examined. This investigation aims to identify the pathogenicity of mutant FOXL2 by studying its altered transcriptional targets. The expression of mutant FOXL2 was reduced in the GCT cell line KGN, and wildtype and mutant FOXL2 were overexpressed in the GCT cell line COV434. Comparisons were made between the transcriptomes of control cells and cells altered by FOXL2 knockdown and overexpression, to detect potential transcriptional targets of mutant FOXL2. Comparisons were made between the transcriptomes of control cells and cells altered by FOXL2 knockdown and overexpression, to detect potential transcriptional targets of mutant FOXL2.
Publication Title
The transcriptional targets of mutant FOXL2 in granulosa cell tumours.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Differential gene expression between naive and activated CD8+ T cells was assessed using microarray analysis to determine target genes for new positron emission tomography (PET) probe screening, in particular for molecular imaging of lymphoid organs and immune activation.
Publication Title
Molecular imaging of lymphoid organs and immune activation by positron emission tomography with a new [18F]-labeled 2'-deoxycytidine analog.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Retinopathy of prematurity (ROP) is a disorder of the developing retina of preterm infants. ROP can lead to blindness due to abnormal angiogenesis that is the result of suspended vascular development and vaso-obliteration leading to severe retinal stress and hypoxia. We tested the hypothesis that a combined treatment with two human progenitor populations, the CD34+ cells, bone marrow-derived, and the endothelial colony-forming cells (ECFCs) synergistically protected the developing retinal vasculature in a murine model of ROP, the oxygen-induced retinopathy (OIR)., CD34+ cells alone, ECFCs alone, or a combination thereof were injected intravitreally at either P5 or P12 and pups were euthanized at P17. Retinas from OIR mice injected with ECFCs or the combined treatment revealed formation of the deep vascular plexus (DVP) while still in hyperoxia, with normal appearing connections between the superficial vascular plexus (SVP) and the DVP. The combination therapy prevented aberrant retinal neovascularization and was more effective anatomically and functionally at rescuing the ischemia phenotype than either cell type alone. The beneficial effect of the cell combination was the result of their ability to orchestrate an acceleration of vascular development and more rapid ensheathment of pericytes on the developing vessels.
Publication Title
Progenitor cell combination normalizes retinal vascular development in the oxygen-induced retinopathy (OIR) model.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
ZFP36L2, zinc finger protein 36, C3H type-like 2 (also known as Brf2, Erf2, Tis11D) is a member of the tristetraprolin (TTP; Zfp36) family of tandem CCCH zinc finger proteins that can bind to AU-rich elements (AREs) in the 3'-untranslated region of mRNAs, leading to their deadenylation and subsequent degradation. We have generated Zfp36l2 knockout mice. Knockout mice were born at the expected Mendelian frequency, but within several weeks of birth they died rather suddenly with pallor and frequent intestinal hemorrhage. These mice exhibited pancytopenia, decreased hematopoietic progenitor cells from fetal liver and yolk sac, and ineffective hematopoietic stem cells. Since ZFP26L2 is likely to function as an ARE-containing mRNA destabilizing protein, we were interested in identifying any abnormally stabilized transcripts in fetal livers from the Zfp36l2 knockout mice whose protein product may directly or indirectly affect hematopoietic stem cell function.
Publication Title
Targeted disruption of Zfp36l2, encoding a CCCH tandem zinc finger RNA-binding protein, results in defective hematopoiesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
In all primary cells analyzed to date, aneuploidy is associated with poor proliferation. Yet, how abnormal karyotypes affect cancer a disease characterized by both aneuploidy and heightened proliferative capacity is largely unknown. Here, I demonstrate that the transcriptional alterations caused by aneuploidy in primary cells are also present in chromosomally-unstable cancer cell lines, but are not common to all aneuploid cancers. Moreover, chromosomally-unstable cancer lines display increased glycolytic and TCA-cycle flux, as is also observed in primary aneuploid cells. The biological response to aneuploidy is associated with cellular stress and slow proliferation, and a 70-gene signature derived from primary aneuploid cells is a strong predictor of increased survival in several cancers. Inversely, a transcriptional signature derived from clonal aneuploidy in tumors correlates with high mitotic activity and poor prognosis. I speculate that there are two types of aneuploidy in cancer: clonal aneuploidy, which is selected during tumor evolution and is associated with robust growth, and sub-clonal aneuploidy, which is caused by chromosomal instability (CIN) and more closely resembles the stressed state of primary aneuploid cells. Nonetheless, CIN is not benign: a subset of genes upregulated in high-CIN cancers predict aggressive disease in human patients in a proliferation-independent manner.
Publication Title
A transcriptional and metabolic signature of primary aneuploidy is present in chromosomally unstable cancer cells and informs clinical prognosis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 32 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219)
Description
Chronic alcohol consumption can lead to alchohol-related brain damage (ARBD). Despite the well known acute effects of alcohol the mechanism responsible for chronic brain damage is largely unknown. Pathologically the major change is the loss of white matter while neuronal loss is mild and restricted to a few areas such as the prefrontal cortex. In order to improve our understanding of ARBD pathogenesis we used microarrays to explore the white matter transcriptome of alcoholics and controls.
Publication Title
Comorbidities, confounders, and the white matter transcriptome in chronic alcoholism.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Danio rerio
- 9 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
Ethanol is a well-known teratogen. While this teratogenic potential is well-characterized clinically, the mechanisms through which ethanol exposure results in developmental defects remain unclear. Here we use the zebrafish model to elucidate eye-specific mechanisms that may underlie ethanol-mediated microphthalmia (reduced eye size), using time-series microarray analysis of gene expression of eye tissues of embryos exposed to 1.5% ethanol vs. untreated embryos. We identified 62 genes differentially expressed in ethanol-treated as compared to control zebrafish eyes from all sampling times over the period of retinal neurogenesis (24-48 hours post-fertilization). Application of the EDGE (extraction of differential gene expression) algorithm identified over 3000 genes differentially expressed over developmental time in ethanol-treated embryo eyes as compared to untreated embryo eyes. These lists included several genes indicating a mis-regulated cellular stress response (heat shock response) due to ethanol exposure. Combined treatment with sub-threshold levels of ethanol and a morpholino (MO) targeting heat shock factor 1 (hsf-1) mRNA resulted in a microphthalmic phenotype, suggesting convergent molecular pathways. Manipulation of the heat shock response by thermal preconditioning partially prevented ethanol-mediated microphthalmia while maintaining Hsf-1 expression. Together these data are consistent with roles for reduced Hsf-1 in mediating microphthalmic effects of embryonic ethanol exposure in zebrafish.
Publication Title
Eye-specific gene expression following embryonic ethanol exposure in zebrafish: roles for heat shock factor 1.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Mesothelia, which cover all coelomic organs and body cavities in vertebrates, perform diverse functions in embryonic and adult life. Yet, mesothelia are traditionally viewed as simple, uniform epithelia.
Publication Title
Autotaxin signaling governs phenotypic heterogeneity in visceral and parietal mesothelia.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina HiSeq 2500
Description
Mutation or deletion of Neurofibromin (NF1), an inhibitor of RAS signaling, frequently occurs in epithelial ovarian cancer (EOC), supporting therapies that target downstream RAS effectors, such as the RAF-MEK-ERK pathway. However, no comprehensive studies have been carried out testing the efficacy of MEK inhibition in NF1-deficient EOC. Here, we performed a detailed characterization of MEK inhibition in NF1-deficient EOC cell lines using kinome profiling and RNA sequencing. Our studies showed MEK inhibitors were ineffective at providing durable growth inhibition in NF1-deficient cells due to kinome reprogramming. MEKi-mediated destabilization of FOSL1 resulted in induced expression of RTKs and their downstream RAF and PI3K signaling overcoming MEKi therapy. MEKi synthetic enhancement screens identified BRD2 and BRD4 as integral mediators of the MEKi-induced RTK signatures. Inhibition of BET proteins using BET bromodomain inhibitors (BETi) blocked MEKi-induced RTK reprogramming, indicating BRD2 and BRD4 represent promising therapeutic targets in combination with MEKi to block resistance due to kinome reprogramming in NF1-deficient EOC. Overall design: Examination of the global effects on transcription in response to trametinib (GSK212) in A1847 cells.
Publication Title
Intrinsic Resistance to MEK Inhibition through BET Protein-Mediated Kinome Reprogramming in NF1-Deficient Ovarian Cancer.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Damage-associated molecular pattern (DAMP) molecules S100A8 and S100A9 with well-known functions in inflammation, tumor growth and metastasis. It has been found to have promote tumor cell proliferation activity at low concentration . However, the mechanism underlying this remains unclear. In the current study, we performed genome expression profiling analysis using the Affymetrix genome wide microarray system to identify broad scale changes in gene expression associated with S100a8 or S100a9 recombinant protein stimulation in murine colon carcinoma cell line CT26.WT.
Publication Title
Inflammation-induced S100A8 activates Id3 and promotes colorectal tumorigenesis.
Sample Metadata Fields
Cell line
View Samples