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GSE21861
Mus musculus
8 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Although the cytokine-inducible transcription factors STAT5a/b promote proliferation of a wide range of cell types, there are cell- and context specific cases in which loss of STAT5a/b results in enhanced cell proliferation. Here we report that loss of STAT5a/b from mouse embryonic fibroblasts (MEFs) leads to enhanced proliferation, which was linked to reduced levels of the cell cycle inhibitor p15INK4B and p21CIP1. We further demonstrate that growth hormone through the transcription factor STAT5a/b enhances expression of the cdkn2B gene and that STAT5a binds to GAS sites within the promoter. We have recently demonstrated that ablation of STAT5a/b from liver results in hepatocellular carcinoma upon a CCl4 insult. We also established that in liver tissue, like in MEFs, STAT5a/b activates expression of the cdkn2B gene. Loss of STAT5a/b led to diminished p15INK4B and increased hepatocyte proliferation. This study for the first time demonstrates that cytokines through STAT5a/b can induce the expression of a key cell cycle inhibitor. These experiments therefore shed a light on the context-specific role of STAT5a/b as tumor suppressors.
Publication Title
The transcription factors signal transducer and activator of transcription 5A (STAT5A) and STAT5B negatively regulate cell proliferation through the activation of cyclin-dependent kinase inhibitor 2b (Cdkn2b) and Cdkn1a expression.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [probe set (exon) version (huex10st)
Description
Using measles virus induced T cell suppression as a model, we established that T cell inhibitory protein isoforms can be produced from alternatively spliced pre-mRNAs as a result of virus-mediated ablation of T cell receptor dependent activation of the phosphatidylinositol-3-kinase (PI3K). To asses production of alternative splice variants in response to PI3K abrogation in T cells at a whole cell level, we performed a Human Exon 1.0 ST Array on RNAs isolated from T cells stimulated only or stimulated after PI3K inhibition. We developed a simple algorithm based on a splicing index to detect genes that undergo alternative splicing (AS) or are differentially regulated (RG) on T cell suppression. Applying our algorithm on this model 9% of the genes were assigned as AS, while only 3% were attributed to RG. Though there are overlaps, AS and RG genes differed with regard to functional regulated at the level of AS or RG were found enriched in different functional groups with AS targeting e. g. extra cellular matrix (ECM)-receptor interaction and focal adhesion, while cytokine-receptor interaction, Jak-STAT and p53 pathways were mainly RG. When combined, AS/RG dependent alterations targeted pathways essential for T cell receptor signaling, cytoskeletal dynamics and cell cycle entry strongly supporting the notion that PI3K abrogations interferes with key T cell activation processes at both levels, and that candidates represented within both categories bear the potential to actively contribute to T cell suppression
Publication Title
Accumulation of splice variants and transcripts in response to PI3K inhibition in T cells.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Caenorhabditis elegans
- 10 Downloadable Samples
Illumina HiSeq 2500
Description
In this study we have investigated the effect of loss of math-33 activity on DAF-16-mediated target gene regulation in C. elegans under conditions of reduced Insulin/IGF-1 signaling (IIS). Using whole nematode RNA sequencing experiments we found that the daf-2(e1370)-mediated induction and repression of DAF-16 target genes was decreased in daf-2(e1370); math-33(tm3561) mutant animals. Our data suggest that the downregulation of endogenous DAF-16 isoforms in the absence of a functional MATH-33 severely affects the global expression of DAF-16 targets when IIS activity is reduced. Therefore, MATH-33 is essential for DAF-16-mediated target gene activation and repression in the context of IIS. Overall design: DAF-16 mediated target gene regulation was analyzed in daf-2(e1370) nematodes and compared to daf-2(e1370); math-33(tm3561) mutant animals. daf-16(mu86); daf-2(e1370); N2 (wild type) and math-33(tm3561) single mutant animals were used as controls.
Publication Title
The Deubiquitylase MATH-33 Controls DAF-16 Stability and Function in Metabolism and Longevity.
Sample Metadata Fields
Specimen part, Subject
View Samples- Arabidopsis thaliana
- 20 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Tissues of Arabidopsis plants overexpressing artificial microRNAs were compared to wild_type and respective target gene mutants (duplicate arrays)
Publication Title
Highly specific gene silencing by artificial microRNAs in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The pre-synaptic protein -synuclein is a key player in the pathogenesis of Parkinson's disease. Together with accumulation and missfolding of -synuclein protofibrils serve as seed structures for the aggregation of numerous proteins in the cytoplasm of neuronal cells, the so-called Lewy bodies. Furthermore, missense mutations in the SNCA gene and gene multiplications lead to autosomal dominant forms of familiar PD. However, so far the exact biological role of -synuclein in normal brain is elusive. To gain more insights into the biological function of this protein we monitored whole genome expression changes in dopaminergic neuroblastoma cells (SH-SY5Y) caused by a 90% reduction of -synuclein by RNA interference.
Publication Title
Microarray expression analysis of human dopaminergic neuroblastoma cells after RNA interference of SNCA--a key player in the pathogenesis of Parkinson's disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 22 Downloadable Samples
- Ion Torrent Proton
Description
We designed a study to investigate immunoediting of an epithelial cancer genome using wildtype and immunodeficient mice, NGS, and analytical pipelines to process and analyze the data. We carried out experiments with wildtype and immunodeficient RAG1-/- mice with transplanted tumors and analyzed longitudinal samples with respect to the genomic landscape and the immunophenotypes of the tumors. Finally, we performed also experiments with anti-PD-L1 antibodies and show how the activation of the PD1-PD-L1 axis modulates immunoediting. MC38 cells were subcutaneously injected into wild-type C57Bl/6 and immunodeficient Rag1-/- mice. Samples were taken at predefined time points and subjected to detailed analysis, including FACS, exome sequencing, RNA sequencing and SNP arrays. Overall design: Samples were taken at predifined time points, in triplicates and subjected to RNA sequencing using Ion Torrent Proton
Publication Title
Targeting immune checkpoints potentiates immunoediting and changes the dynamics of tumor evolution.
Sample Metadata Fields
Subject, Time
View Samples- Danio rerio
- 415 Downloadable Samples
- Illumina HiSeq 2500
Description
SMART-seq2 was performed on single cells isolated from visually staged zebrafish embryos. Overall design: Samples were all sequenced in one batch. Some were generated with a 5'' UMI-tagged method, and others are full-length SMART-seq2.
Publication Title
Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis.
Sample Metadata Fields
Subject
View Samples- Mus musculus, Homo sapiens
- 30 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Characterisation of cisplatin-induced transcriptomics responses in primary mouse hepatocytes, HepG2 cells and mouse embryonic stem cells shows conservation of regulating transcription factor networks.
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Danio rerio
- 28 Downloadable Samples
- NextSeq 500
Description
Wild-type zebrafish embryos were mechanically dissociated and profiled using Drop-seq Overall design: Drop-seq was performed on 28 groups of 20-40 visually staged, mechanically dissociated embryos. Samples were combined and sequenced in batches DS2-DS5.
Publication Title
Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- IlluminaHiSeq2500
Description
Substantial effort is currently devoted to identifying cancer-associated alterations using genomics. Here, we show that standard blood collection procedures rapidly change the transcriptional and post-transcriptional landscapes of hematopoietic cells, resulting in biased activation of specific biological pathways, up-regulation of pseudogenes, antisense RNAs, and unannotated coding isoforms, and RNA surveillance inhibition. Affected genes include common mutational targets and thousands of other genes participating in processes such as chromatin modification, RNA splicing, T and B cell activation, and NF-?B signaling. The majority of published leukemic transcriptomes exhibit signals of this incubation-induced dysregulation, explaining up to 40% of differences in gene expression and alternative splicing between leukemias and reference normal transcriptomes. The effects of sample processing are particularly evident in pan-cancer analyses. We provide biomarkers that detect prolonged incubation of individual samples, and show that keeping blood on ice markedly reduces changes to the transcriptome. In addition to highlighting the potentially confounding effects of technical artifacts in cancer genomics data, our study emphasizes the need to survey the diversity of normal as well as neoplastic cells when characterizing tumors. This study is complemented by GSE61410: transcriptomic profiling of bone marrow cells from healthy individuals. Overall design: Peripheral blood mononuclear cells (PBMCs) were isolated from four healthy individuals, following an ex vivo incubation of variable length at either room temperature or on ice. RNA transcriptomes were measured using the Illumina HiSeq.
Publication Title
Sample processing obscures cancer-specific alterations in leukemic transcriptomes.
Sample Metadata Fields
No sample metadata fields
View Samples