Filters
Technology
Platform
GSE79625
Homo sapiens
4 Downloadable Samples
Affymetrix Human Genome U219 Array (hgu219)
Description
LMO2 overexpressing transgenic mouse models suggest an accumulation of immature T-cell progenitors in the thymus as main pre-leukemic event. The effects of LMO2 overexpression on human T-cell development in vivo, however, are unknown. Here we report studies of a humanized mouse model transplanted with LMO2 transduced human hematopoietic stem and progenitor cells. The effects of LMO2 overexpression were confined to the T-cell lineage although initially multipotent cells were transduced. Three effects of LMO2 on human T-cell development were observed: 1) a block at the DN/ISP stage, 2) an accumulation of CD4+CD8+ double positive CD3- cells and 3) an altered CD8/CD4 ratio with enhanced peripheral T lymphocytes
Publication Title
Overexpression of LMO2 causes aberrant human T-Cell development in vivo by three potentially distinct cellular mechanisms.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 166 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Cellular immunotherapy has proven to be effective in the treatment of hematological cancers by donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation and more recently by targeted therapy with chimeric antigen or T-cell receptor-engineered T-cells. However, dependent on the tissue distribution of the antigens that are targeted, anti-tumor responses can be accompanied by undesired side effects. Therefore, detailed tissue distribution analysis is essential to estimate efficacy and toxicity of candidate targets for immunotherapy of hematological malignancies. In this study, we performed microarray gene expression analysis of hematological malignancies of different origins, healthy hematopoietic cells and various non-hematopoietic cell types from organs that are often targeted in detrimental immune responses after allogeneic stem cell transplantation leading to graft-versus-host disease. Non-hematopoietic cells were also cultured in the presence of IFN- to analyze gene expression under inflammatory circumstances. Gene expression was investigated by Illumina HT12.0 microarrays and quality control analysis was performed to confirm the cell-type origin and exclude contamination of non-hematopoietic cell samples with peripheral blood cells. Microarray data were validated by quantitative RT-PCR showing strong correlation between both platforms. Detailed gene expression profiles were generated for various minor histocompatibility antigens and B-cell surface antigens to illustrate the value of the microarray dataset to estimate efficacy and toxicity of candidate targets for immunotherapy. In conclusion, our microarray database provides a relevant platform to analyze and select candidate antigens with hematopoietic (lineage)-restricted expression as potential targets for immunotherapy of hematological cancers.
Publication Title
Integrated Whole Genome and Transcriptome Analysis Identified a Therapeutic Minor Histocompatibility Antigen in a Splice Variant of ITGB2.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 97 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Many innovative techniques and scientific improvements are available to tackle societal concerns, like public health safety and confining the risk of cancerous exposure to chemicals, but have not been thoroughly tested and implicated yet. We investigated if microRNA and mRNA transcription profiles can be implemented in a short-term carcinogen classifier assay. Our study is additionally focusing on the drawbacks of present-day carcinogen screening strategies and also aims to contribute to a more ethical approach towards animal use and welfare within risk assessment. Since current in vitro and in silico assays are still not able to mimic the in vivo situation accurately we set out to develop an alternative short-term in vivo assay. Five genotoxic, seven non-genotoxic and five non-carcinogen exposure studies were used to investigate if murine hepatic microRNA and mNA profiles after 7-day exposure are suitable tools to classify carcinogens. Classification analyses showed that a small transcript set, consisting of both microRNA and mRNA, is able to classify the genotoxic, non-genotoxic and non-carcinogens tested with 100% accuracy. The results indicate that microRNAs have the potential to be used as transcriptional classifiers and that a short-term transcriptional classifier assay in mice can be a powerful tool in carcinogenicity risk assessment.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Mus musculus
- 60 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
To gain insight in the kinetics and interplay of the predominant transcriptional responses of DNA damage signalling pathways in undifferentiated cells, mouse embryonic stem cells were exposed to cisplatin at four different time points (2, 4, 8 and 24 hr) and concentrations (1, 2, 5 and 10 uM). RNA was isolated and subjected to genome-wide expression profiling.
Publication Title
A portrait of cisplatin-induced transcriptional changes in mouse embryonic stem cells reveals a dominant p53-like response.
Sample Metadata Fields
Specimen part, Compound, Time
View Samples- Mus musculus
- 10 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The aim of the present study was to compare, on a statistical basis, the performance of different microarray platforms to detect differences in gene expression in a realistic and challenging biological setting. Gene expression profiles in the hippocampus of five wild-type and five transgenic C-doublecortin-like kinase mice were evaluated with five microarray platforms: Applied Biosystems, Affymetrix, Agilent, Illumina and home-spotted oligonucleotide arrays. We observed considerable overlap between the different platforms, the overlap being better detectable with significance level-based ranking than with a p-value based cut-off. Confirming the qualitative agreement between platforms, Pathway analysis consistently demonstrated aberrances in GABA-ergic signalling in the transgenic mice, even though pathways were represented by only partially overlapping genes on the different platforms.
Publication Title
Can subtle changes in gene expression be consistently detected with different microarray platforms?
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Mycosis fungoides (MF), the most common cutaneous T-cell lymphoma (CTCL), is a malignancy of mature, skin-homing T cells. Szary syndrome (Sz) is often considered to represent a leukemic phase of MF. In this study the pattern of numerical chromosomal alterations in MF tumor samples was defined using array-based CGH; simultaneously gene expression was analyzed using microarrays. Highly recurrent chromosomal alterations in MF include copy number gain of 7q36, 7q21-7q22 and loss of 5q13 and 9p21. This pattern characteristic of MF differs markedly from chromosomal alterations observed in Sz. Integration of data from array-based CGH and gene expression analysis yielded several candidate genes with potential relevance in the pathogenesis of MF. We confirmed that the FASTK and SKAP1 genes, residing in loci with recurrent gain, demonstrated increased expression. The RB1 and DLEU1 tumor suppressor genes showed diminished expression associated with loss. In addition, it was found that presence of chromosomal alterations on 9p21, 8q24 and 1q21-1q22 was associated with poor prognosis in patients with MF. This study provides novel insight into genetic alterations underlying MF. Furthermore, our analysis uncovered genomic differences between MF and Sz, which suggest that the molecular pathogenesis and therefore therapeutic requirements of these CTCLs may be distinct.
Publication Title
Oncogenomic analysis of mycosis fungoides reveals major differences with Sezary syndrome.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Genome-wide expression studies were performed on dermal fibroblasts from Sotos syndrome patients with a confirmed NSD1 abnormality and compared with age-sex matched controls.
Publication Title
Sotos syndrome is associated with deregulation of the MAPK/ERK-signaling pathway.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Homo sapiens
- 36 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
In cervical cancer, an important mechanism by which tumour cells escape immune surveillance is loss of HLA class I, enabling tumours to evade recognition and lysis by cytotoxic T lymphocytes. Some tumours, however, escape from immune surveillance without accumulating defects in antigen presentation. We hypothesized that tumours with no or partial loss of HLA class I develop alternative mechanisms to prevent immune surveillance. To investigate this hypothesis, genome-wide expression profiling using Illumina arrays was performed on cervical squamous cell carcinomas showing overall loss of HLA class I, partial and normal HLA class I protein expression. Statistical analyses revealed no significant differences in gene expression between tumours with partial (n = 11) and normal HLA class I expression (n = 10). Comparison of tumours with normal/partial HLA class I expression (n = 21) with those with overall loss of HLA class I expression (n = 11) identified 150 differentially expressed genes. Most of these genes were involved in the defense response (n = 27), and, in particular, inflammatory and acute phase responses. Especially SerpinA1 and SerpinA3 were found to be upregulated in HLA positive tumours (3.6 and 8.2 fold, respectively), and this was confirmed by real-time PCR and immunohistochemistry. In a group of 117 tumours, high SerpinA1 and SerpinA3 expression in association with normal/partial HLA expression correlated significantly with poor overall survival (p = 0.035 and p = 0.05, respectively). This study shows that HLA positive tumours are characterized by a higher expression of genes associated with an inflammatory profile and that expression of the acute phase proteins SerpinA1 and SerpinA3 in HLA positive tumours is associated with worse prognosis.
Publication Title
Elevated expression of SerpinA1 and SerpinA3 in HLA-positive cervical carcinoma.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 30 Downloadable Samples
- Illumina ratRef-12 v1.0 expression beadchip
Description
Huntingtons disease (HD) is a devastating disease for which currently no therapy is available. It is a progressive autosomal dominant neurodegenerative disorder that is caused by a CAG repeat expansion in the HD gene, resulting in an expansion of polyglutamines at the N-terminal end of the encoded protein, designated huntingtin, and the accumulation of cytoplasmic and nuclear aggregates. Not only is there a loss of normal huntingtin function, upon expansion of the CAG repeat there is also a gain of toxic function of the huntingtin protein and this affects a wide range of cellular processes. To identify groups of genes that could play a role in the pathology of Huntingtons disease, we studied mRNA changes in an inducible PC12 model of Huntingtons disease before and after aggregates became visible. This is the first study to show the involvement Nrf2-responsive genes in the oxidative stress response in HD. Oxidative stress related transcripts were altered in expression suggesting a protective response in cells expressing mutant huntingtin at an early stage of cellular pathology. Furthermore, there was a down-regulation of catecholamine biosynthesis resulting in lower dopamine levels in culture. Our results further demonstrate an early impairment of transcription, the cytoskeleton, ion channels and receptors. Given the pathogenic impact of oxidative stress and neuroinflammation, the Nrf2-ARE signaling pathway is an attractive therapeutic target for neurodegenerative diseases.
Publication Title
Mutant huntingtin activates Nrf2-responsive genes and impairs dopamine synthesis in a PC12 model of Huntington's disease.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 26 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
Oculopharyngeal muscular dystrophy (OPMD) is a late-onset progressive muscle disorder caused by a poly-alanine expansion mutation in PABPN1. The hallmark of OPMD is the accumulation of the mutant protein in insoluble nuclear inclusions. The molecular mechanisms associated with disease onset and progression are unknown. We performed a high-throughput cross-species transcriptome study of affected muscles from two OPMD animal models and from patients at pre-symptomatic and symptomatic stages. The most consistently and significantly OPMD-deregulated pathway across species is the ubiquitin-proteasome system (UPS). By analyzing expression profiles, we found that the majority of OPMD-deregulated genes are age-associated. Based on expression trends, disease onset can be separated from progression; the expression profiles of the proteasome-encoding genes are associated with onset but not with progression. In a muscle cell model, proteasome inhibition and the stimulation of immunoproteasome specifically affect the accumulation and aggregation of mutant PABPN1. We suggest that proteasome down-regulation during muscle aging triggers the accumulation of expPABPN1 that in turn enhances proteasome deregulation and leads to intranuclear inclusions (INI) formation.
Publication Title
Deregulation of the ubiquitin-proteasome system is the predominant molecular pathology in OPMD animal models and patients.
Sample Metadata Fields
Sex, Age, Disease, Disease stage
View Samples