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GSE58173
Homo sapiens
17 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Objective: In idiopathic inflammatory myopathies (IIM) infiltration of immune cells into muscle and upregulation of MHC-I expression implies increased antigen presentation and involvement of the proteasome system. To decipher the role of immunoproteasomes in myositis, we investigated individual cell types and muscle tissues and focused on possible immune triggers. Methods: Expression of constitutive (PSMB5, -6, -7) and corresponding immunoproteasomal subunits (PSMB8, -9, -10) was analyzed by real-time RT-PCR in muscle biopsies and sorted peripheral blood cells of patients with IIM, non-inflammatory myopathies (NIM) and healthy donors (HD). Protein analysis in muscle biopsies was performed by western blot. Affymetrix HG-U133 platform derived transcriptome data from biopsies of different muscle diseases and from immune cell types as well as monocyte stimulation experiments were used for validation, coregulation and coexpression analyses. Results: Real-time RT-PCR revealed significantly increased expression of immunoproteasomal subunits (PSMB8/-9/-10) in DC, monocytes and CD8+ T-cells in IIM. In muscle biopsies, the immunosubunits were elevated in IIM compared to NIM and exceeded levels of matched blood samples. Proteins of PSMB8 and -9 were found only in IIM but not NIM muscle biopsies. Reanalysis of 78 myositis and 20 healthy muscle transcriptomes confirmed these results and revealed involvement of the antigen processing and presentation pathway. Comparison with reference profiles of sorted immune cells and healthy muscle confirmed upregulation of PSMB8 and -9 in myositis biopsies beyond infiltration related changes. This upregulation correlated highest with STAT1, IRF1 and IFN expression. Elevation of T-cell specific transcripts in active IIM muscles was accompanied by increased expression of DC and monocyte marker genes and thus reflects the cell type specific involvement observed in peripheral blood. Conclusions: Immunoproteasomes seem to indicate IIM activity and suggest that dominant involvement of antigen processing and presentation may qualify these diseases exemplarily for the evolving therapeutic concepts of immunoproteasome specific inhibition.
Publication Title
Upregulation of immunoproteasome subunits in myositis indicates active inflammation with involvement of antigen presenting cells, CD8 T-cells and IFNΓ.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Clariom S Human array (clariomshuman)
Description
Metastasis of human tumours to LNs is a universally negative prognostic factor. LN stromal cells (SCs) play a crucial role in enabling T cell responses, and since tumour metastases modulate their structure and function, this interaction may suppress immune responses to tumour antigens. However the SC subpopulations that respond to infiltration of malignant cells into human LNs have not been defined. Using microarray, we sought to assess gene expression profiles of two distinct SC subpopulations isolated from melanoma-infiltrated LNs.
Publication Title
Distinctive Subpopulations of Stromal Cells Are Present in Human Lymph Nodes Infiltrated with Melanoma.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The maintenance of the TFH phenotype depends on continuous signals via ICOS. For a global assessment of differences in gene expression after interruption of the ICOS pathway a genome wide transcriptome analysis was performed. We used the OT-II adoptive transfer system to isolate antigen-specific TFH cells (day 6 after immunization) after short-term (6 hours) blockade of the ICOS pathway using a monoclonal antibody against ICOS-L.
Publication Title
ICOS maintains the T follicular helper cell phenotype by down-regulating Krüppel-like factor 2.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Homo sapiens
- 127 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2), Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Identification of a new gene regulatory circuit involving B cell receptor activated signaling using a combined analysis of experimental, clinical and global gene expression data.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Time
View Samples- Homo sapiens
- 33 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
To discover new essential regulatory pathways in B lymphoma cells a combined analysis of experimental and clinical high throughput data was performed. Among others, a specific cluster of coherently expressed genes named BCR.1 was identified in primary lymphoma samples. These coherently expressed genes are suppressed by -IgM treatment of lymphoma cells in vitro. This B cell receptor activation leads to a G2 phase prolongation, delayed entry into the M phase, an overall diminished capacity of the cells to enter into mitosis and defects in metaphases. Cytogenetic changes are detected under long term -IgM treatment. Furthermore, an inverse correlation of BCR.1 genes with c-Myc coregulated genes in distinct groups of lymphoma patients is observed. In addition to the impact of c-Myc in the regulation of cell cycle regulators, BCR.1 genes are regulated by a combined action of IKK2, MAPK14 and JNK. Finally, the BCR.1 index discriminates activated B cell like and germinal centre B cell like diffuse large B cell lymphoma. Therefore, a new regulatory circuit is described affecting cell cycle and chromosome instability in B cells.
Publication Title
Identification of a new gene regulatory circuit involving B cell receptor activated signaling using a combined analysis of experimental, clinical and global gene expression data.
Sample Metadata Fields
Specimen part, Time
View Samples- Homo sapiens
- 20 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
To discover new essential regulatory pathways in B lymphoma cells a combined analysis of experimental and clinical high throughput data was performed. Among others, a specific cluster of coherently expressed genes named BCR.1 was identified in primary lymphoma samples. These coherently expressed genes are suppressed by -IgM treatement of lymphoma cells in vitro. This B cell receptor activation leads to a G2 phase prolongation, delayed entry into the M phase, an overall diminished capacity of the cells to enter into mitosis and defects in metaphases. Cytogenetic changes are detected under long term -IgM treatment. Furthermore, an inverse correlation of BCR.1 genes with c-Myc coregulated genes in distinct groups of lymphoma patients is observed. In addition to the impact of c-Myc in the regulation of cell cycle regulators, BCR.1 genes are regulated by a combined action of IKK2, MAPK14 and JNK. Finally, the BCR.1 index discriminates activated B cell like and germinal centre B cell like diffuse large B cell lymphoma. Therefore, a new regulatory circuit is described affecting cell cycle and chromosome instability in B cells.
Publication Title
Identification of a new gene regulatory circuit involving B cell receptor activated signaling using a combined analysis of experimental, clinical and global gene expression data.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 10 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Plant reproduction depends on the concerted activation of many genes to assure the correct communication between pollen and pistil. Here we queried the whole transcriptome of Arabidopsis thaliana in order to identify genes with specific reproductive functions.
Publication Title
Whole genome analysis of gene expression reveals coordinated activation of signaling and metabolic pathways during pollen-pistil interactions in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 9 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Models for tumorigenesis can be made by transforming normal cells with defined genetic elements. This allows us to determine that adrenocortical tumor development and progression follows a multistep model. Morever, we demonstrated that the order of genetic events has a great consequence on the phenotype of the resultant tumor. We performed transcriptomic analysis using cDNA microarrays to identify the molecular signature that might explain the distinctive in vivo phenotypes observed in response to both orders of the mutational events.
Publication Title
Acquisition order of Ras and p53 gene alterations defines distinct adrenocortical tumor phenotypes.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 98 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Acute Myeloid Leukemia AML is a cancer in which the process of normal cell hematopoietic differentiation is disrupted. Evidence exists that AML comprises a hierarchy with leukemic stem cells giving rise to more differentiated, but immature and functionally incompetent populations. The similarity of these AML subpopulations to normal stages of hematopoietic differentiation has not been dissected comprehensively at the transcriptional level. Here we introduce Normal Memory Analysis (NorMA), a data analysis method that extracts from omic data the remnants of the healthy normal-like phenotype. Applying NorMA to gene expression data from AML uncovered a wealth of information in the normal-like component of data: the normal hematopoietic memory of AML tumor cells. We found significant variation within the patient population, and we found strong association of this normal hematopoietic memory with survival. We found that undifferentiated NorMA phenotype has significantly worse survival than differentiated NorMA phenotype, showing that the NorMA classification of tumors captures a biologically meaningful stratification of patients, with highly significant survival association. Patients with NorMA phenotype in the undifferentiated Hematopoietic Stem Cell HSC stage had the worst survival, with median survival time under 6 months. We further found significant survival differences between tumor groups with differentiated NorMA phenotype, depending on their hematopoietic path: AML patients with NorMA phenotype in megakaryocyte-erythroid progenitor MEP stage had significantly better survival than those with NorMA phenotype in granulocyte-macrophage progenitor GMP stage. Thus NorMA produced a stratification of AML cohorts by differentiation stage, with significant outcome differences. It also provided clean molecular signatures for these stages. NorMA can be used in many other contexts, to explore for example the tumor cell of origin, or disease predisposition.
Publication Title
An LSC epigenetic signature is largely mutation independent and implicates the HOXA cluster in AML pathogenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 48 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Utilizing glycerol and cardiotoxin (CTX) injections in the tibialis anterior muscles of M. musculus provides models of skeletal muscle damages followed by skeletal muscle regeneration. In particular, glycerol-induced muscle regeneration is known to be associated with ectopic adipogenesis. We characterized genome-wide expression profiles of tibialis anterior muscles from wild-type mice injured by either glycerol or CTX injection. Our goal was to detect gene expression changes during the time course of glycerol-induced and CTX-induced muscle regeneration models, that can lead to ectopic adipocyte accumulation.
Publication Title
Genomic profiling reveals that transient adipogenic activation is a hallmark of mouse models of skeletal muscle regeneration.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples