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GSE22186
Homo sapiens
8 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Role of p53 serine 46 in p53 target gene regulation.
Sample Metadata Fields
Specimen part, Cell line, Compound
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
The tumor suppressor p53 plays a crucial role in cellular growth control inducing a plethora of cellular response pathways. The molecular mechanisms that discriminate between the distinct p53-responses towards different stress treatments have remained largely elusive. Here, we have analyzed the p53-regulated pathways induced by two chemotherapeutical treatments, Actinomycin D inducing growth arrest and Etoposide resulting in apoptosis. We found that the genome-wide p53-binding patterns are almost identical upon both treatments notwithstanding transcriptional differences that we observed in genome-wide transcriptome analysis. To assess the role of post-translational modifications in target gene choice and activation we investigated the extent of phosphorylation of Serine 46 of p53 bound to DNA (p53-pS46), a modification that has been linked to apoptosis-pathways, and the extent of phosphorylation of Serine 15 (p53-pS15), a general p53-activation mark. Interestingly, the overall extent of S46 phosphorylation of p53 bound to DNA is considerably higher in cells directed towards apoptosis while the degree of phosphorylation at S15 of DNA bound p53 remains highly similar upon both treatments. Moreover, our data suggest that, following different chemotherapeutical treatments, the extent of chromatin-associated p53 phosphorylated at S46 but not at pS15 is higher on certain apoptosis related target genes, including the BAX and PUMA genes. These data provide evidence that cell fate decisions are not made primarily on the level of general p53 DNA-binding, but possibly through post-translational modifications of chromatin bound p53.
Publication Title
Role of p53 serine 46 in p53 target gene regulation.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 502 Downloadable Samples
Illumina HiSeq 2500
Description
This dataset contains collected RNASeq data of 552 samples from the GOYA clinical trial. Overall design: The GOYA trial tested the efficacy of Gazyva (GA101) compared with Rituxan (Rituximab) in first line, untreated DLBCL patients. Patients were randomized 1:1 to either G or R combined with a CHOP chemotherapy backbone. Tumor samples were collected at baseline, RNA was isolated using RNA-Access, and RNASeq was run with TruSeq (Illumina) RNASeq.
Publication Title
PD-L1 and tumor-associated macrophages in de novo DLBCL.
Sample Metadata Fields
Treatment, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
RNA was isolated from fluorescence activated cell sorted (FACS) Lgr5-GFP+ and Lgr5-GFP- from aged matched subcutaneously implanted Apcmin/+;KrasLSL-G12D/+;VillinCre; Lgr5DTReGFP;p53KO (AKVPL) and Apcmin/+;KrasLSL-G12D/+;VillinCre; Lgr5DTReGFP;p53KO;SMAD4KO (AKVPSL) intestinal tumours. "SAMPLE_ID" sample characteristic is a sample identifier internal to Genentech. The ID of this project in Genentech''s ExpressionPlot database is PRJ0009421 Overall design: Gene expression profiling of Lgr5+ and Lgr5- tumour cells from AKVPL and AKVPSL murine derived intestinal tumours
Publication Title
A distinct role for Lgr5<sup>+</sup> stem cells in primary and metastatic colon cancer.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 61 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We profiled 40 NHL cell lines to determine gene expression patterns and molecular subtypes.
Publication Title
Therapeutic potential of an anti-CD79b antibody-drug conjugate, anti-CD79b-vc-MMAE, for the treatment of non-Hodgkin lymphoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Hereditary sensory and autonomic neuropathy type I (HSAN-I) is neurological disorder characterized by distal sensory neuron dysfunction, frequent infections, and ulcerative mutilations. It remains unknown if HSAN-I directly dampens protective immunity. Here we report that HSAN-I-causing mutations of serine palmitoyltransferase long chain base subunit 2 (SPTLC2) affect human T cell responses. T cell antigenic stimulation and inflammation induce SPTLC2 expression. Murine T cell-specific ablation of Sptlc2 fundamentally impairs antiviral T cell survival and effector function. Mechanistically, SPTLC2-deficiency reduces sphingolipid biosynthetic flux and causes a prolonged activation of the mechanistic target of rapamycin complex 1 (mTORC1), endoplasmic reticulum (ER) stress and CD8+ T cell death. Antiviral CD8+ T cell responses are restored by supplementing sphingolipids and pharmacologically inhibiting ER stress-induced cell death. Our study reveals that SPTLC2 underpins protective adaptive immunity by translating extracellular stimuli into intracellular anabolic signals and reducing cellular stress to maintain metabolic reprogramming sustainability Overall design: Triplicates of each group were used for RNA-seq. Four groups were studied: Wild-type and SPTLC2-deficient CD8+ T cells, harvested from either naïve mice (D0) or mice infected with LCMV Armstrong 8 days earlier (D8).
Publication Title
Loss of Neurological Disease HSAN-I-Associated Gene SPTLC2 Impairs CD8<sup>+</sup> T Cell Responses to Infection by Inhibiting T Cell Metabolic Fitness.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We profiled human DLBCL tumor samples (FF and FFPE matched pairs) to identify the transcripts which are less prone to degradation in FFPE
Publication Title
CD40 pathway activation status predicts response to CD40 therapy in diffuse large B cell lymphoma.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 23 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We profiled human DLBCL patient samples to discover predictive biomarkers
Publication Title
CD40 pathway activation status predicts response to CD40 therapy in diffuse large B cell lymphoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 146 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This dataset encompassing the profiles of 150 lung cancer tumors was developed to serve as test dataset in the SBV IMPROVER Diagnostic Signature Challenge (sbvimprover.com). The aim of this subchallenge was to verify that it is possible to extract a robust diagnostic signature from gene expression data that can identify stages of different types of lung cancer. Participants were asked to develop and submit a classifier that can stratify lung cancer patients in one of four groups Stage 1 of Adenocarcinoma (AC Stage 1), Stage 2 of Adenocarcinoma (AC Stage 2), Stage 1 of Squamous cell carcinoma (SCC Stage 1) or Stage 2 of Squamous cell carcinoma (SCC Stage 2). The classifier could be built by using any publicly available gene expression data with related histopathological information and was tested on the independent dataset described here.
Publication Title
Strengths and limitations of microarray-based phenotype prediction: lessons learned from the IMPROVER Diagnostic Signature Challenge.
Sample Metadata Fields
Sex, Specimen part, Disease stage, Race
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Renal hypoxia is widespread in acute kidney injury (AKI) of various aetiologies. Hypoxia adaptation, conferred through the hypoxia-inducible factor (HIF), appears to be insufficient. Here we show that HIF activation in renal tubules through Pax8-rtTA-based inducible knockout of von Hippel-Lindau protein (VHL-KO) protects from rhabdomyolysis-induced AKI. In this model, histological observations indicate that injury mainly affects proximal convoluted tubules, with 5% necrosis at d1 and 40% necrosis at d2. HIF-1alpha up-regulation in distal tubules reflects renal hypoxia. However, lack of HIF in proximal tubules suggests insufficient adaptation by HIF.
Publication Title
Tubular von Hippel-Lindau knockout protects against rhabdomyolysis-induced AKI.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples