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GSE76296
Mus musculus
8 Downloadable Samples
Illumina MouseRef-8 v2.0 expression beadchip
Description
We report the expression anaysis of neural stem cells lacking p53, ATMIN, or both. p53-deficent cells form GBM, which is significanly delayed in the absence of ATMIN.
Publication Title
Inactivation of the ATMIN/ATM pathway protects against glioblastoma formation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 769 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We used microarrays to measure the expression levels of genes in irradiated immortalized B cells, lymphoblastoid cells, from members of Centre d'Etude du Polymorphisme Humain (CEPH) Utah pedigrees. Data were collected for cells at baseline and 2 hours and 6 hours after exposure to 10 Gy of ionizing radiation (IR).
Publication Title
Genetic variation in radiation-induced cell death.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this study we compared the effects of IL-2, IL-15, and IL-21 on the gene expression, activation of cell signaling pathways, and functional properties of cells derived from the CD4+ cutaneous T-cell lymphoma (CTCL). Whereas both IL-2 and IL-15 that signal through receptors that share the common gamma chain and the beta chain modulated the expression of >1,000 genes, IL-21 that signals via the receptor also containing gamma chain up-regulated <40 genes. All three cytokines induced tyrosine phosphorylation of Jak1 and Jak3. However, only IL-2 and IL-15 strongly activated STAT5, PI3K/Akt, and MEK/ERK signaling pathways. In contrast, IL-21 selectively activated STAT3. Whereas all three cytokines protected CTCL cells from apoptosis, only IL-2 and IL-15 promoted their proliferation. The effects of the cytokine stimulation were Jak3- and Jak1-kinase dependent. These findings document the vastly different impact of IL-2 and IL-15 vs. IL-21 on malignant CD4+ T cells. They also suggest two novel therapeutic approaches to CTCL and, possibly, other CD4+ T cell lymphomas: inhibition of the Jak1/Jak3 kinase complex and, given the known strong immunostimulatory properties of IL-21 on CD8+ T, NK, and B cells, application of this cytokine to boost an immune response against malignant CD4+ T cells.
Publication Title
Differential effects of interleukin-2 and interleukin-15 versus interleukin-21 on CD4+ cutaneous T-cell lymphoma cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this study we compared the effects of IL-2, IL-15, and IL-21 on the gene expression, activation of cell signaling pathways, and functional properties of cells derived from the CD4+ cutaneous T-cell lymphoma (CTCL). Whereas both IL-2 and IL-15 that signal through receptors that share the common gamma chain and the beta chain modulated the expression of >1,000 genes, IL-21 that signals via the receptor also containing gamma chain up-regulated <40 genes. All three cytokines induced tyrosine phosphorylation of Jak1 and Jak3. However, only IL-2 and IL-15 strongly activated STAT5, PI3K/Akt, and MEK/ERK signaling pathways. In contrast, IL-21 selectively activated STAT3. Whereas all three cytokines protected CTCL cells from apoptosis, only IL-2 and IL-15 promoted their proliferation. The effects of the cytokine stimulation were Jak3- and Jak1-kinase dependent. These findings document the vastly different impact of IL-2 and IL-15 vs. IL-21 on malignant CD4+ T cells. They also suggest two novel therapeutic approaches to CTCL and, possibly, other CD4+ T cell lymphomas: inhibition of the Jak1/Jak3 kinase complex and, given the known strong immunostimulatory properties of IL-21 on CD8+ T, NK, and B cells, application of this cytokine to boost an immune response against malignant CD4+ T cells.
Publication Title
Differential effects of interleukin-2 and interleukin-15 versus interleukin-21 on CD4+ cutaneous T-cell lymphoma cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
In this study we compared the effects of ALK inhibitor on the gene expression, activation of cell signaling pathways, and functional properties of cells derived from a patient with Anaplastic Large Cell Lymphoma. we used microarrays to map the genome-wide gene expression patterns in ALK+TCL cells in response to ALK inhibition.
Publication Title
Malignant transformation of CD4+ T lymphocytes mediated by oncogenic kinase NPM/ALK recapitulates IL-2-induced cell signaling and gene expression reprogramming.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 70 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The primary goal of toxicology and safety testing is to identify agents that have the potential to cause adverse effects in humans. Unfortunately, many of these tests have not changed significantly in the past 30 years and most are inefficient, costly, and rely heavily on the use of animals. The rodent cancer bioassay is one of these safety tests and was originally established as a screen to identify potential carcinogens that would be further analyzed in human epidemiological studies. Today, the rodent cancer bioassay has evolved into the primary means to determine the carcinogenic potential of a chemical and generate quantitative information on dose-response behavior in chemical risk assessments. Due to the resource-intensive nature of these studies, each bioassay costs $2 to $4 million and takes over three years to complete. Over the past 30 years, only 1,468 chemicals have been tested in a rodent cancer bioassay. By comparison, approximately 9,000 chemicals are used by industry in quantities greater than 10,000 lbs and nearly 90,000 chemicals have been inventoried by the U.S. Environmental Protection Agency as part of the Toxic Substances Control Act. Given the disparity between the number of chemicals tested in a rodent cancer bioassay and the number of chemicals used by industry, a more efficient and economical system of identifying chemical carcinogens needs to be developed.
Publication Title
Application of genomic biomarkers to predict increased lung tumor incidence in 2-year rodent cancer bioassays.
Sample Metadata Fields
Sex, Age, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
Illumina HiSeq 2000
Description
The capacity of cancer cells to undergo epithelial mesenchymal trans-differentiation has been implicated as a factor driving metastasis, through the acquisition of enhanced migratory/invasive cell programs and the engagement of anti-apoptotic mechanisms promoting drug and radiation resistance. Our aim was to define molecular signaling changes associated with mesenchymal trans-differentiation in two KRas mutant NSCLC models. We focused on central transcription and epigenetic regulators predicted to be important for mesenchymal cell survival. Overall design: Haley, J.A., Haughney, E., Ullman, E., Bean, J., Haley, J.D.* and Fink, M.Y. (2014) 'Altered Transcriptional Control Networks with Trans-Differentiation of Isogenic Mutant KRas NSCLC Models' Front. Oncology, doi/10.3389/fonc.2014.00344.
Publication Title
Altered Transcriptional Control Networks with Trans-Differentiation of Isogenic Mutant-KRas NSCLC Models.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Ligand-mediated activation of the nuclear hormone receptor PPAR gamma lowers blood pressure and improves glucose tolerance in humans. Two naturally occurring mutations (P467L, V290M) in the ligand binding domain of PPAR gamma have been described in humans that lead to severe insulin resistance and hypertension. Experimental evidence suggests that these mutant versions of PPAR gamma act in a dominant negative fashion. To better understand the molecular mechanisms underlying PPAR gamma action in the vasculature, we determined the global gene expression profile in primary aortic endothelial cells in response to endothelial cell specific expression of a dominant negative isoform of PPAR gamma (V290M).
Publication Title
Endothelium-specific interference with peroxisome proliferator activated receptor gamma causes cerebral vascular dysfunction in response to a high-fat diet.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 35 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare NGS-derived brain transcriptome profiling (RNA-seq) in neuropathic region specific Gaucher mouse brain compared with WT and Isofagamine treated mice of the same age and background and secondly to identify the DEmiRNA associated with the DEmRNA before and after treatment This will give us some insights to see if miRNA is also involved in the the regulation of the expression of the genes involved in the disease process before and after treatment. Methods: 42-45 days old 4L;C*, wild-type (WT) and Isofagamine treated 4L;C* mouse brain were generated by deep sequencing, in triplicate, using IlluminaHiseq. The sequence reads that passed quality filters were analyzed at the gene level with two methods: Burrows–Wheeler Aligner (BWA) followed and TopHat followed by DESeq. qRT–PCR validation was performed using TaqMan and SYBR Green assays Overall design: Regional brain mRNA profiles of ~42 -days old wild type (WT) and 4L;C* an d Isofagamine treated mice were generated by deep sequencing, in triplicate, using IlluminaHi Seq.
Publication Title
Signatures of post-zygotic structural genetic aberrations in the cells of histologically normal breast tissue that can predispose to sporadic breast cancer.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 32 Downloadable Samples
- NextSeq 500
Description
Polycomb repressive complex-2 (PRC2) is a group of proteins that play important role during development and in cell differentiation. PRC2 is a histone-modifying complex that catalyses methylation of lysine 27 of histone H3 (H3K27me3) at differentiation genes leading to their transcriptional repression. JARID2 is a co-factor of PRC2 and is important for targeting PRC2 to chromatin as well as modulating its activity. Here, we show that in many human cells, including human epidermal keratinocytes, JARID2 predominantly exists as a novel low molecular weight form, which lacks the N-terminal PRC2-interacting domain (?N-JARID2). We show that ?N-JARID2 is a cleaved product of full-length JARID2 spanning the C-terminal conserved region consisting of jumonji domains. JARID2 knockout in keratinocytes results in up-regulation of cell cycle genes and repression of many epidermal differentiation genes. Surprisingly, repression of epidermal differentiation genes in JARID2-null keratinocytes can be relieved by expression of ?N-JARID2 suggesting that this form promotes activation of these genes and has opposing function to that of PRC2 in regulation of differentiation. We propose that a switch from expression of full-length JARID2 to ?N-JARID2 is important for the up-regulation of genes during differentiation. Overall design: RNA-seq analysis of Wildtype and JARID2-null keratinocytes (HaCaTs) on day 0 and day 3 of calcium induced differentiation.
Publication Title
A novel form of JARID2 is required for differentiation in lineage-committed cells.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples