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GSE6344
Homo sapiens
40 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Although renal cell carcinoma (RCC) is the sixth-leading cause of cancer death, the molecular events leading to disease onset and progression are not well understood. Genomic profiling of clear cell RCC (cRCC) patients indicated that loss of a negative regulator of the Wnt pathway, secreted frizzled-related protein 1 (sFRP1), occurred in the majority of more than 100 patients tested. To our knowledge, this is the first report of loss of sFRP1 expression in patients diagnosed with cRCC; this loss occurs in early stage cRCC, suggesting that it may be an important early event in renal carcinogenesis. Genomic profiling of patient matched normal and cRCC tissues identified Wnt regulated genes to be aberrantly increased in cRCC tissues suggesting sFRP1 suppresses Wnt signaling in cRCC. In order to test the hypothesis that sFRP1 acts as a tumor suppressor in cRCC, we have stably expressed sFRP1 in cRCC cells. sFRP1 expression in cRCC cells resulted in decreased growth in cell culture, inhibition of anchorage-independent growth, and decreased tumor volume in a nude mouse model. Together these data suggest an important role for sFRP1 as a tumor suppressor in cRCC.
Publication Title
Secreted frizzled-related protein 1 loss contributes to tumor phenotype of clear cell renal cell carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 42 Downloadable Samples
Illumina HiSeq 2500
Description
Precise control of mRNA decay is fundamental for robust yet not exaggerated inflammatory responses to pathogens. Parameters determining the specificity and extent of mRNA degradation within the entire inflammation-associated transcriptome remain incompletely understood. Using transcriptome-wide high resolution occupancy assessment of the mRNA-destabilizing protein TTP, a major inflammation-limiting factor, we qualitatively and quantitatively characterize TTP binding positions and functionally relate them to TTP-dependent mRNA decay in immunostimulated macrophages. We identify pervasive TTP binding with incompletely penetrant linkage to mRNA destabilization. A necessary but not sufficient feature of TTP-mediated mRNA destabilization is binding to 3’ untranslated regions (UTRs). Mapping of binding positions of the mRNA-stabilizing protein HuR in activated macrophages revealed that TTP and HuR binding sites in 3’ UTRs occur mostly in different transcripts implicating only a limited co-regulation of inflammatory mRNAs by these proteins. Remarkably, we identify robust and widespread TTP binding to introns of stable transcripts. Nuclear TTP is associated with spliced-out introns and maintained in the nucleus throughout the inflammatory response. Our study establishes a functional annotation of binding positions dictating TTP-dependent mRNA decay in immunostimulated macrophages. The findings allow navigating the transcriptome-wide landscape of RNA elements controlling inflammation. Overall design: Experiment comparing RNA decay rates in WT and TTP-/- macrophages at LPS 3 h and 6 h. Transcription was blocked with actinomycin D for 0, 45 or 90 min. Decay rates was calculated using linear model.
Publication Title
Tristetraprolin binding site atlas in the macrophage transcriptome reveals a switch for inflammation resolution.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
We have investigated the p53-dependent stress response in medium spiny neurons (MSNs) that degenerate in Huntingtons disease. To induce p53 signaling cascade, we have genetically inactivated by the Cre/loxP system the essential RNA polymerase I (Pol I) transcription factor TIF-IA, leading to stabilization of p53 and induction of p53-dependent apoptosis.
Publication Title
A neuroprotective phase precedes striatal degeneration upon nucleolar stress.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
Precise control of mRNA decay is fundamental for robust yet not exaggerated inflammatory responses to pathogens. Parameters determining the specificity and extent of mRNA degradation within the entire inflammation-associated transcriptome remain incompletely understood. Using transcriptome-wide high resolution occupancy assessment of the mRNA-destabilizing protein TTP, a major inflammation-limiting factor, we qualitatively and quantitatively characterize TTP binding positions and functionally relate them to TTP-dependent mRNA decay in immunostimulated macrophages. We identify pervasive TTP binding with incompletely penetrant linkage to mRNA destabilization. A necessary but not sufficient feature of TTP-mediated mRNA destabilization is binding to 3’ untranslated regions (UTRs). Mapping of binding positions of the mRNA-stabilizing protein HuR in activated macrophages revealed that TTP and HuR binding sites in 3’ UTRs occur mostly in different transcripts implicating only a limited co-regulation of inflammatory mRNAs by these proteins. Remarkably, we identify robust and widespread TTP binding to introns of stable transcripts. Nuclear TTP is associated with spliced-out introns and maintained in the nucleus throughout the inflammatory response. Our study establishes a functional annotation of binding positions dictating TTP-dependent mRNA decay in immunostimulated macrophages. The findings allow navigating the transcriptome-wide landscape of RNA elements controlling inflammation. Overall design: RNA-Seq of RNA isolated from murine bone marrow derived macrophages (WT or TTP-deficient) stimulated for 6 h with LPS
Publication Title
Tristetraprolin binding site atlas in the macrophage transcriptome reveals a switch for inflammation resolution.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 13 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The thymus is extremely sensitive to damage but also has a remarkable ability to repair itself. However, the mechanisms underlying this endogenous regeneration remain poorly understood and this capacity diminishes considerably with age. To identify alternate regeneration pathways in the thymus, we performed an unbiased transcriptome analysis of the non-hematopoietic (CD45-) stromal cell compartment of the thymus, which is less sensitive to thymic damage compared to the CD45+ hematopoietic compartment.
Publication Title
Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The thymus is extremely sensitive to damage but also has a remarkable ability to repair itself. However, the mechanisms underlying this endogenous regeneration remain poorly understood and this capacity diminishes considerably with age. To identify alternate regeneration pathways in the thymus, we performed an unbiased transcriptome analysis of the non-hematopoietic (CD45-) stromal cell compartment of the thymus, which is less sensitive to thymic damage compared to the CD45+ hematopoietic compartment.
Publication Title
Production of BMP4 by endothelial cells is crucial for endogenous thymic regeneration.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 1 Downloadable Sample
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
IPH-926 is an anticancer drug-resistant tumor cell line derived from a chemo-refractory human infiltrating lobular breast cancer (ILBC). IPH-926 ILBC cells were subjected to gene expression profiling using an Affymetrix HG U133 Plus 2.0 array.
Publication Title
ABCB1/MDR1 contributes to the anticancer drug-resistant phenotype of IPH-926 human lobular breast cancer cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Human solid tumors contain rare cancer side population (SP) cells, which expel the fluorescencent dye H33342 and display cancer stem cell characteristics. Transcriptional profiling of cancer SP cells isolated by H33342 fluorescence analysis is a newly emerging approach to discover cancer stem cell markers and aberrant differentiation pathways. Using Affymetrix expression microarrays this study investigated differential gene expression between SP and non-SP (NSP) cells isolated from the CAL-51 human mammary carcinoma cell line.
Publication Title
Down-regulation of the fetal stem cell factor SOX17 by H33342: a mechanism responsible for differential gene expression in breast cancer side population cells.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Primary HBE cells were stimulated with IL-22 and IL-17, and gene expression was studied using an Affymetrix platform microarray, in order to investigate which genes may be upregulated or downregulated in response to these cytokines. Of particular interest was the host defense genes such as antimicrobial peptides, which have been shown to be upregulated by IL-22 and IL-17 in skin keratinocytes.
Publication Title
IL-22 mediates mucosal host defense against Gram-negative bacterial pneumonia.
Sample Metadata Fields
No sample metadata fields
View Samples