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accession-icon GSE48970
Contribution of the STAT1alpha and STAT1beta isoforms to IFN-gamma mediated innate immunity
  • organism-icon Mus musculus
  • sample-icon 48 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Gene 1.0 ST Array (mogene10st)

Description

The transcription factor STAT1 is essential for interferon- (IFN) mediated protective immunity in humans and mice. Two splice isoforms of STAT1, STAT1 and STAT1, differ with regard to a C-terminal transactivation domain, which is absent in STAT1. Dimers of STAT1 are therefore considered transcriptionally inactive and potential competitive inhibitors of STAT1. Contrasting this view, generation and analysis of mice deficient for either STAT1 or STAT1 demonstrated transcriptional activity of the STAT1 isoform and its enhancement of innate immunity. Gene expression profiling in primary cells revealed overlapping, but also non-redundant and gene-specific activities of STAT1 and STAT1 in response to IFN. Consistently, both isoforms mediated protective, IFN-dependent immunity against the bacterium Listeria monocytogenes, although with remarkably different efficiency. In contrast, STAT1 and STAT1 were largely redundant for transcriptional responses to IFN/ and for IFN/-dependent antiviral activity. Collectively, our data shed new light on how STAT1 isoforms contribute to antimicrobial immunity.

Publication Title

STAT1β is not dominant negative and is capable of contributing to gamma interferon-dependent innate immunity.

Sample Metadata Fields

Specimen part

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accession-icon GSE22865
CHAC1 mRNA expression is a strong prognostic biomarker in breast and ovarian cancer
  • organism-icon Homo sapiens
  • sample-icon 11 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Extracellular, cancer-specific methylated DNA has been shown to be a prognostic marker when detected in serum or plasma. In this study we investigated the effect of treating cancer cells with differentially methylated CpG DNA. When breast cancer cell lines were treated with methylated CpG DNA, a consistent upregulation of CHAC1 mRNA expression was observed. CHAC1 was recently described to be a novel component of the unfolded protein response pathway. To elucidate the role of CHAC1 mRNA expression in cancer in more detail, we analyzed expression of this gene in breast (n=107) and ovarian cancer (n=107) and found a strong correlation with tumor differentiation. Poorly differentiated tumors exhibited higher CHAC1 expression levels (p=0.004 for breast and p=0.031 for ovarian cancer). Additionally, hormone receptor (HR)-negative breast cancers (p<0.001) and advanced stage disease ovarian cancers (p=0.026) also demonstrated high CHAC1 mRNA levels. mRNA expression analysis of the two known CHAC1 isoforms showed a strong association of expression above the median with poor outcome in breast cancer patients in a multivariate analysis (isoform a: relative risk (RR) of death 3.2 (95% CI 1.6-6.5; p<0.01); RR of relapse 3.9 (95% CI 1.6-9.8; p<0.01); isoform b: relative risk (RR) of death 3.5 (95% CI 1.6-7.3; p<0.01); RR of relapse 6.6 (95% CI 2.4-18.5; p<0.01)). Univariate analysis in ovarian cancer showed that CHAC1 mRNA expression above the median was associated with a poor relapse free survival (p=0.03). In younger ovarian cancer patients (age < median age), a high CHAC1 mRNA expression was associated with overall survival (p=0.007) and relapse free survival (p=0.015). Finally, we show that downregulation of CHAC1 by small interfering RNA suppressed breast cancer cell migration and proliferation, whereas overexpression resulted in an observed increase in these cellular behaviours. This is the first report demonstrating that a gene (CHAC1) whose expression is triggered by methylated, but not unmethylated DNA, is involved in tumour biology.

Publication Title

Elevated mRNA expression of CHAC1 splicing variants is associated with poor outcome for breast and ovarian cancer patients.

Sample Metadata Fields

Specimen part, Cell line, Treatment

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accession-icon GSE4475
A Biologic Definition of Burkitt's Lymphoma from Transcriptional and Genomic Profiling
  • organism-icon Homo sapiens
  • sample-icon 219 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A Array (hgu133a)

Description

The distinction between the Burkitt lymphoma and diffuse large B-cell lymphoma is imprecise using current diagnostic criteria. We applied transcriptional and genomic profiling to molecularly define Burkitt lymphoma. Gene expression profiling employing Affymetrix GeneChips (U133A) was performed in 220 mature aggressive B-cell lymphomas, including a core group of eight Burkitt lymphomas, which fulfilled all diagnostic criteria of the WHO classification. A molecular signature of Burkitt lymphoma was generated. Chromosomal abnormalities were detected by interphase fluorescence in-situ hybridization and array comparative genomic hybridization. The molecular Burkitt lymphoma signature identified 44 cases. Fifteen of these cases lacked a morphology typical for Burkitt/Burkitt-like lymphoma. The vast majority (88%) of the 176 lymphomas without the molecular Burkitt lymphoma signature represented diffuse large B-cell lymphomas. In 20% of these cases a MYC break was detectable which was associated with complex chromosomal changes. Our molecular definition of Burkitt lymphoma sharpens and extends the spectrum of Burkitt lymphoma. In mature aggressive B-cell lymphomas without a Burkitt lymphoma signature, a chromosomal break in the MYC locus proved to be associated with adverse clinical outcome.

Publication Title

A biologic definition of Burkitt's lymphoma from transcriptional and genomic profiling.

Sample Metadata Fields

Sex, Age

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accession-icon E-MEXP-1921
Transcription profiling of Drosophila mechanoreceptor-rich tissue compared mechanoreceptor-poor tissue shows DCX-EMAPis required for mechanoreception in sensory cilia
  • organism-icon Drosophila melanogaster
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Drosophila Genome Array (drosgenome1)

Description

Determining which genes are expressed in mechanoreceptor-rich tissue (pedicel) compared mechanoreceptor-poor tissue (capitellum) and a neuronal subtraction control (thoracic ganglion) in Drosophila melanogaster

Publication Title

A doublecortin containing microtubule-associated protein is implicated in mechanotransduction in Drosophila sensory cilia.

Sample Metadata Fields

Sex, Age, Specimen part

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accession-icon GSE11289
Activation of peroxisome proliferator-activated receptor alpha in human peripheral blood mononuclear cells
  • organism-icon Homo sapiens
  • sample-icon 12 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)

Description

Background: Peripheral blood mononuclear cells (PBMCs) are relatively easily obtainable cells in humans. Gene expression profiles of PBMCs have been shown to reflect the pathological and physiological state of a person. Recently, we showed that the nuclear receptor peroxisome proliferator-activated receptor alpha (PPAR) has a functional role in human PBMCs during fasting. However, the extent of the role of PPAR in human PBMCs remains unclear. In this study, we therefore performed gene expression profiling of PBMCs incubated with the specific PPAR ligand WY14,643. Results: Incubation of PBMCs with WY14,643 for 12 hours resulted in a differential expression of 1,373 of the 13,080 genes expressed in the PBMCs. Gene expression profiles showed a clear individual response to PPAR activation between six healthy human blood donors, which was not the result of the nutritional status of the donors. Pathway analysis showed that genes in fatty acid metabolism, primarily in -oxidation were up-regulated upon activation of PPAR with WY14,643, and genes in several amino acid metabolism pathways were down-regulated. Conclusions: This study shows that PPAR in human PBMCs regulates fatty acid and amino acid metabolism. In addition, PBMC gene expression profiles show individual responses to WY14,643 activation. We show that PBMCs are a suitable model to study changes in PPAR activation in healthy humans.

Publication Title

Activation of peroxisome proliferator-activated receptor alpha in human peripheral blood mononuclear cells reveals an individual gene expression profile response.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE6497
Expression profile of syngeneic (sTX) and allogeneic kidney (aTX) transplantation compared to control (ctr) kidneys
  • organism-icon Rattus norvegicus
  • sample-icon 15 Downloadable Samples
  • Technology Badge Icon Affymetrix Rat Genome 230 2.0 Array (rat2302)

Description

Microarray analyses provide a powerful approach to identify gene expression alterations following kidney transplantation. However, the heterogeneity of human kidney transplant specimens and the variation in sample preparation precludes conclusions regarding the underlying mechanisms of the observed alterations. We used a well defined experimental rat kidney transplantation model with consistent transplant and sample preparation procedures to analyze genome wide changes in gene expression after syngeneic (sTX) and allogeneic transplantation (aTX) four days after transplantation. Both interventions were associated with dramatic changes in gene expression. Genes and Pathways related to immune response were extremely up regulated after aTX. Several of the up regulated genes have been described by other groups and we are able to proof this in one study. But several genes are reported for the first time to be up regulated in expression after renal aTX. The function of these genes in acute rejection process has to be evaluated. On the other hand the up regulation of regulatory or protective genes indicates that regulatory mechanism are activated after aTX trying to down regulate the immune response or protect the tissue against the immune system. The study is capable to serve as a representative study in aTX mediated gene expression by covering the known transcriptional changes reported by other groups and identification of novel markers and pathways. Further analysis of the duplicated datasets by other groups can help for a better understanding of the mechanisms mediated by acute rejection and thereby increase the therapeutic threatment.

Publication Title

Activation of counter-regulatory mechanisms in a rat renal acute rejection model.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE15757
PRC2 in Ewing tumors
  • organism-icon Homo sapiens
  • sample-icon 9 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Genome U133A Array (hgu133a)

Description

We found the PRC2 component EZH2 to be upregulated by the pathognomonic fusion oncogene EWS-FLI1 in Ewing tumors and mesenchymal stem cells (Richter GH et al., Proc Natl Acad Sci U S A. 2009;106:5324-9). Downregulation of EZH2 by RNA interference in Ewing tumor cell lines suppressed oncogenic transformation in vitro and in vivo. These data suggest that EZH2 might play a central role in Ewing Tumor pathology.

Publication Title

Epigenetic maintenance of stemness and malignancy in peripheral neuroectodermal tumors by EZH2.

Sample Metadata Fields

No sample metadata fields

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accession-icon GSE61786
Loss of the Histone Methyltransferase EZH2 induces Resistance to Multiple Drugs in Acute Myeloid Leukemia
  • organism-icon Homo sapiens
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia.

Sample Metadata Fields

Specimen part, Cell line

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accession-icon GSE61715
Loss of the Histone Methyltransferase EZH2 induces Resistance to Multiple Drugs in Acute Myeloid Leukemia
  • organism-icon Homo sapiens
  • sample-icon 4 Downloadable Samples
  • Technology Badge Icon Affymetrix Human Gene 1.0 ST Array (hugene10st)

Description

Here, we analyzed global gene expression changes that were associated with drug resistance in Acute Myeloid Leukemia using the Affymetrix microarray platform.

Publication Title

Loss of the histone methyltransferase EZH2 induces resistance to multiple drugs in acute myeloid leukemia.

Sample Metadata Fields

Specimen part, Cell line

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accession-icon GSE30649
Detailed transcriptomics analysis of the effect of dietary fatty acids on gene regulation in the murine heart [superseries]
  • organism-icon Mus musculus
  • sample-icon 55 Downloadable Samples
  • Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

Description

This SuperSeries is composed of the SubSeries listed below.

Publication Title

Detailed transcriptomics analysis of the effect of dietary fatty acids on gene expression in the heart.

Sample Metadata Fields

Sex, Treatment

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refine.bio is a repository of uniformly processed and normalized, ready-to-use transcriptome data from publicly available sources. refine.bio is a project of the Childhood Cancer Data Lab (CCDL)

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Cite refine.bio

Casey S. Greene, Dongbo Hu, Richard W. W. Jones, Stephanie Liu, David S. Mejia, Rob Patro, Stephen R. Piccolo, Ariel Rodriguez Romero, Hirak Sarkar, Candace L. Savonen, Jaclyn N. Taroni, William E. Vauclain, Deepashree Venkatesh Prasad, Kurt G. Wheeler. refine.bio: a resource of uniformly processed publicly available gene expression datasets.
URL: https://www.refine.bio

Note that the contributor list is in alphabetical order as we prepare a manuscript for submission.

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