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Platform
GSE40160
Homo sapiens
10 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The pathogenesis of classical Hodgkin lymphoma (cHL), the most common lymphoma in the young, is still enigmatic, largely because its Hodgkin and Reed-Sternberg (HRS) tumor cells are rare in the involved lymph node and therefore difficult to analyze. Here, by overcoming this technical challenge and performing for the first time a genome-wide transcriptional analysis of microdissected HRS cells in comparison to other B-cell lymphomas, cHL lines and normal B-cell subsets, we show that they differ extensively from the usually studied cHL cell lines, that the lost B-cell identity of cHLs is not linked to the acquisition of a plasma cell-like gene expression program, and that Epstein-Barr virus infection of HRS cells has a minor transcriptional influence on the established cHL clone. Moreover, although cHL appears a distinct lymphoma entity overall, HRS cells of its histological subtypes diverged in their similarity to other related lymphomas. Unexpectedly, we identified two molecular subgroups of cHL associated to differential strengths of the transcription factor activity of the NOTCH1, MYC and IRF4 proto-oncogenes. Finally, HRS cells display deregulated expression of several genes potentially highly relevant to lymphoma pathogenesis, including silencing of the apoptosis-inducer BIK and of INPP5D, an inhibitor of the PI3K-driven oncogenic pathway.
Publication Title
Analyzing primary Hodgkin and Reed-Sternberg cells to capture the molecular and cellular pathogenesis of classical Hodgkin lymphoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Deficiency of the human short stature homeobox-containing gene (SHOX) has been identified in several disorders characterized by reduced height and skeletal anomalies such as Turner, Leri-Weill and Langer syndrome as well as idiopathic short stature. Although highly conserved in vertebrates, rodents lack a SHOX orthologue.
Publication Title
Identification of novel SHOX target genes in the developing limb using a transgenic mouse model.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 94 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 94 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
We used the Infinium HumanHT-12 platform to profile gene expression in 79 primary, untreated high-grade soft tissue sarcomas, representing eight relevant subtypes, two non-neoplastic fat samples and 13 representative sarcoma cell lines.
Publication Title
Integrative DNA methylation and gene expression analysis in high-grade soft tissue sarcomas.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We used microarrays to assess gene expression changes in cells with siRNA-mediated knockdown of OPG compared to normal cells. Furthermore, we used microarrays to assess gene expression in cells treated with either RANKL or TRAIL compared to vehicle-treated cells.
Publication Title
No influence of OPG and its ligands, RANKL and TRAIL, on proliferation and regulation of the calcification process in primary human vascular smooth muscle cells.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Drosophila melanogaster
- 5 Downloadable Samples
Illumina Genome Analyzer II
Description
In Drosophila, PIWI proteins and bound PIWI interacting RNAs (piRNAs) form the core of a small RNA mediated defense system against selfish genetic elements. Within germline cells piRNAs are processed from piRNA clusters and transposons to be loaded into Piwi/Aubergine/AGO3 and a subset of piRNAs undergoes target dependent amplification. In contrast, gonadal somatic support cells express only Piwi, lack signs of piRNA amplification and exhibit primary piRNA biogenesis from piRNA clusters. Neither piRNA processing/loading nor Piwi mediated target silencing is understood at the genetic, cellular or molecular level. We developed an in vivo RNAi assay for the somatic piRNA pathway and identified the RNA helicase Armitage, the Tudor domain containing RNA helicase Yb and the putative nuclease Zucchini as essential factors for primary piRNA biogenesis. Lack of any of these proteins leads to transposon de-silencing, to a collapse in piRNA levels and to a failure in Piwi nuclear accumulation. We show that Armitage and Yb interact physically and co-localize in cytoplasmic Yb-bodies, which flank P-bodies. Loss of Zucchini leads to an accumulation of Piwi and Armitage in Yb-bodies indicating that Yb-bodies are sites of primary piRNA biogenesis. Overall design: small RNA libraries were prepared from Piwi immuno-precipitates of five different genotypes
Publication Title
An in vivo RNAi assay identifies major genetic and cellular requirements for primary piRNA biogenesis in Drosophila.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 14 Downloadable Samples
- IlluminaHiSeq2000
Description
We have employed gene expression profiling in order to identify targets of transcriptional response to stress in resting mouse Swiss 3T3 fibroblasts, either untreated (control) or treated with anisomycin for 3 or 6 hours to induce the p38/MAP kinase pathway. In order determine transcriptional effects dependent on MSK1/2 kinase activity, H89 inhibitor was used in the study. Overall design: Serum starved (72 h 0.2% FCS) mouse 3T3 cells were treated with anisomycin (188.5 nM) for 3 h or 6h (in duplicates) either with or without 15-min pre-treatment with MSK1/2 inhibitor H89 (10 uM). Untreated, serum-starved cells were used as a control. RNA was collected and gene expression profiling using strand-specific RNA-seq was performed.
Publication Title
H3S28 phosphorylation is a hallmark of the transcriptional response to cellular stress.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Genome-wide transcriptome analyses have allowed for systems- level insights into gene regulatory networks. Due to the limited depth of quantitative proteomics, however, our understanding of post-transcriptional gene regulation and its effects on protein complex stoichiometry are lagging behind. Here, we employ deep sequencing and iTRAQ technology to determine transcript and protein expression changes of a Drosophila brain tumour model at near genome-wide resolution. In total, we quantify more than 6,200 tissue-specific proteins, corresponding to about 70% of all transcribed protein-coding genes. Using our integrated data set, we demonstrate that post-transcriptional gene regulation varies considerably with biological function and is surprisingly high for genes regulating transcription. We combine our quantitative data with protein-protein interaction data and show that post-transcriptional mechanisms significantly enhance co-regulation of protein complex subunits beyond transcriptional co-regulation. Interestingly, our results suggest that only about 11% of the annotated Drosophila protein complexes are co-regulated in the brain. Finally, we refine the composition of some of these core protein complexes by analysing the co-regulation of potential subunits. Our comprehensive transcriptome and proteome data provide a rich resource for quantitative biology and offer novel insights into understanding post- transcriptional gene regulation in a tumour model. Overall design: Transcriptomes of 1-3 day old adult female Drosophila melanogaster heads of control and brat mutant were generated by deep sequencing, in triplicate, using Illumina GAIIx.
Publication Title
Transcriptome and proteome quantification of a tumor model provides novel insights into post-transcriptional gene regulation.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
We have employed gene expression profiling in order to identify targets of transcriptional response to stress in resting mouse Swiss 3T3 fibroblasts, either untreated (control) or treated with anisomycin to induce the p38/MAP kinase pathway. Overall design: Serum starved (72 h 0.2% FCS) mouse 3T3 cells were treated with anisomycin (188.5 nM) for 1 h (in duplicates). Untreated, serum-starved cells were used as a control. RNA was collected and gene expression profiling using strand-specific RNA-seq was performed.
Publication Title
H3S28 phosphorylation is a hallmark of the transcriptional response to cellular stress.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Illumina Genome Analyzer II
Description
PIWI proteins and their bound piRNAs form the core of a gonad specific small RNA silencing pathway in animals that protects the genome against the deleterious activity of transposable elements. Recent studies linked the piRNA pathway to TUDOR biology, where TUDOR domains of various proteins recognize and bind symmetrically methylated Arginine residues in PIWI proteins. We systematically analyzed the Drosophila TUDOR protein family and identified three previously not characterized TUDOR domain-containing genes (CG4771, CG14303 and CG11133) as essential piRNA pathway members. We characterized CG4771 (Avocado) in detail and demonstrate a critical role for this protein during primary piRNA biogenesis in somatic and germline cells of the ovary. Avocado physically and/or genetically interacts with the primary pathway components Piwi, Armitage, Yb and Zucchini. Avocado also interacts with the Tdrd12 orthologs CG11133 and CG31755, which are essential for primary piRNA biogenesis in the germline and probably functionally replace the related and soma specific factor Yb. Overall design: small RNA libraries were prepared from total RNA isolation of 8 different genotypes
Publication Title
A systematic analysis of Drosophila TUDOR domain-containing proteins identifies Vreteno and the Tdrd12 family as essential primary piRNA pathway factors.
Sample Metadata Fields
Specimen part, Subject
View Samples