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GSE73483
Homo sapiens
14 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
PAX3-FOXO1 is a fusion transcription factor characteristic for the majority of alveolar rhabdomyosarcoma tumors. It is the main oncogenic driver and deregulates expression of PAX3 target genes.
Publication Title
Comparative expression profiling identifies an in vivo target gene signature with TFAP2B as a mediator of the survival function of PAX3/FKHR.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 5 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Comparison of gene expression profile of Ewing sarcoma cells which have an exchange of the endogenous EWS/FLI1 to either wild-type or a turnover-deficient mutant EWS/FLI1. Most target genes are saturated as only a few target genes are soly driven by increasing protein amount.
Publication Title
Proteasomal Degradation of the EWS-FLI1 Fusion Protein Is Regulated by a Single Lysine Residue.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
We aimed to find gene signatures associated with different subgroups of alveolar rhabdomyosarcoma cell lines defined by differences in detection of pro-apoptotic stress
Publication Title
FGFR4 signaling couples to Bim and not Bmf to discriminate subsets of alveolar rhabdomyosarcoma cells.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
We established gene expression profiles of diagnostic bone marrow samples of monozygotic twins with acute lymphoblastic leukemia. We established technical duplicates for each twin.
Publication Title
Prenatal origin of separate evolution of leukemia in identical twins.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Ewing sarcomas (ES) are highly malignant, osteolytic bone or soft tissue tumors, which are characterized by early metastasis into lung and bone. Genetically, ES are defined by balanced chromosomal EWS/ETS translocations, which give rise to chimeric proteins (EWS-ETS) that generate an oncogenic transcriptional program associated with altered epigenetic marks throughout the genome. By use of an inhibitor (JQ1) blocking BET bromodomain binding proteins (BRDs) we strikingly observed a strong down-regulation of the predominant EWS-ETS protein EWS/FLI1 in a dose dependent manner. Microarray analysis further revealed JQ1 treatment to block a typical ES associated expression program. The effect on this expression program could be mimicked by RNA interference with BRD3 or BRD4 expression, indicating that the EWS/FLI1 mediated expression profile is at least in part mediated via such epigenetic readers. Consequently, contact dependent and independent proliferation of different ES lines was strongly inhibited. Mechanistically, treatment of ES resulted in a partial arrest of the cell cycle as well as induction of apoptosis. Tumor development was suppressed dose dependently in a xeno-transplant model in immune deficient mice, overall indicating that ES may be susceptible to treatment with epigenetic inhibitors blocking BET bromodomain activity and the associated pathognomonic EWS-ETS transcriptional program in ES.
Publication Title
Targeting the EWS-ETS transcriptional program by BET bromodomain inhibition in Ewing sarcoma.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 32 Downloadable Samples
Illumina HiSeq 1500
Description
Mesenchymal stromal cells (MSC) are crucial components of the bone marrow (BM) microenvironment essential for regulating self-renewal, survival and differentiation of hematopoietic stem/progenitor cells (HSPC) in the stem cell niche. MSC are functionally and phenotypically altered in myelodysplastic syndromes (MDS), contributing to disease progression. MDS MSC do not harbor recurrent genetic alterations but have been shown to exhibit an altered methylome compared to MSC from healthy controls. We examined growth, differentiation and HSPC-supporting capacity of ex vivo expanded MSC from MDS patients in comparison to age-matched healthy controls after direct treatment in vitro with the hypomethylating agent azacitidine (AZA). We show that AZA exerts a direct effect on MSC by modulating their differentiation potential. Osteogenesis was significantly boosted in healthy MSC while adipogenesis was inhibited in both healthy and MDS MSC. In co-culture experiments, both AZA treated MDS MSC and healthy MSC exhibited enhanced support of non-clonal HSPC which was associated with increased cell cycle induction. Conversely, clonal MDS HSPC were inhibited by contact with AZA treated MSC. RNA-sequencing analyses of stromal cells revealed changes in pathways essential for HSPC support as well as in immune regulatory pathways. In sum, our data demonstrate that AZA treatment of stromal cells leads to upregulation of HSPC-supportive genes and cell cycle induction in co-cultured healthy HSPC, resulting in a proliferative advantage over clonal HSPC. Thus, restoration of functional hematopoiesis by AZA may be driven by activated stromal support factors in MSC providing cell cycle cues to healthy HSPC. Overall design: RNA sequencing was performed on a mesenchymal stromal cell line (EL08-1D2), either untreated or treated with Azacitidine [(-)AZA vs. (+)AZA].
Publication Title
Direct modulation of the bone marrow mesenchymal stromal cell compartment by azacitidine enhances healthy hematopoiesis.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 52 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Wilms tumor (nephroblastoma) is a pediatric kidney tumor that arises from renal progenitor cells. Since the blastemal type is associated with adverse prognosis, we characterized such Wilms tumors by exome and transcriptome analysis. We detected novel, recurrent somatic mutations affecting the SIX1/2 SALL1 pathway implicated in kidney development, the DROSHA/DGCR8 microprocessor genes as well as alterations in MYCN and TP53, the latter being strongly associated with dismal outcome. The DROSHA mutations impair the RNase III domains, while DGCR8 exhibits stereotypic E518K mutations in the RNA binding domain - both may skew miRNA representation. SIX1 and SIX2 mutations affect a single hotspot (Q177R) in the homeodomain indicative of a dominant effect. In larger cohorts, these mutations cluster in blastemal and chemotherapy-induced regressive tumors that likely derive from blastemal cells and these are characterized by generally higher SIX1/2 expression. These findings broaden the spectrum of human cancer genes and may open new avenues for stratification and therapeutic leads for Wilms tumors.
Publication Title
Mutations in the SIX1/2 pathway and the DROSHA/DGCR8 miRNA microprocessor complex underlie high-risk blastemal type Wilms tumors.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
The underlying relation between Parkinson disease (PD) etiopathology and its major risk factor, aging, is largely unknown. The nature of the specific age-related mechanisms promoting PD onset is experimentally difficult to elucidate because aging is a highly complex process contributed by multiple factors. Recent evidence, however, established a strong and causative link between genome stability and aging. To investigate a possible nexus between DNA damage accumulation, aging, and PD we examined DNA repair pathways associated with aging in laboratory animal models and human cases. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that NER-defective mice exhibit typical PD-like pathological alterations, including decreased dopaminergic innervation in the striatum, increased phospho-synuclein levels, and defects in mitochondrial respiration. NER mouse mutants are also more sensitive to the prototypical PD toxin MPTP and their transcriptomic landscape shares important similarities with that of PD patients. Overall, our results demonstrate that specific defects in DNA repair impact the dopaminergic system, are associated with human PD pathology, and might therefore constitute a novel risk factor for PD by affecting the aging process. Overall design: In total 8 samples were analyzed, 4 controls and 4 Ercc1 mutants.
Publication Title
Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 12 Downloadable Samples
- Illumina HiSeq 2500
Description
miRNA-Sequencing was performed on human aortic valve interestitial cells (AVICs) exposed to 14% stretch at 1 hz or static conditions for 24h. Overall design: Six static control and six samples exposed to cyclic stretch 14% for 24h
Publication Title
The stretch responsive microRNA miR-148a-3p is a novel repressor of IKBKB, NF-κB signaling, and inflammatory gene expression in human aortic valve cells.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
AVICs were exposed to cyclic stretch to examine the role of mechanical stimuli on gene expression
Publication Title
The stretch responsive microRNA miR-148a-3p is a novel repressor of IKBKB, NF-κB signaling, and inflammatory gene expression in human aortic valve cells.
Sample Metadata Fields
Specimen part
View Samples