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GSE47643
Mus musculus
12 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
PreB cells were analyzed for differences in gene expression before and after the overexpression of miR-221. In order to dissect possible targets for the miR-221, gene expression profiles of preB cells un-induced or induced for the miR-221 expression after 8, 16 and 24 hours were compared. All induction time-points, e.g. after 8, 16 and 24 hours were compared to un-induced preB cells and to each other group.
Publication Title
SiPaGene: A new repository for instant online retrieval, sharing and meta-analyses of GeneChip expression data.
Sample Metadata Fields
Specimen part
View Samples- 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
- 74 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
Many cytokines are involved in the pathogenesis of autoimmune diseases and are recognized as relevant therapeutic targets to attenuate inflammation, such as TNF in RA and IFN/ in SLE. To relate the transcriptional imprinting of cytokines in a cell type-specific and disease-specific manner, we generated gene-expression profiles from peripheral monocytes of SLE and RA patients and compared them to in vitro-generated signatures induced by TNF, IFN2a and IFN. Monocytes from SLE and RA patients revealed disease-specific gene-expression profiles. In vitro-generated signatures induced by IFN2a and IFN showed similar profiles that only partially overlapped with those induced by TNF. Comparisons between disease-specific and in vitro-generated signatures identified cytokine-regulated genes in SLE and RA with qualitative and quantitative differences. The IFN-responses in SLE and RA were found to be regulated in a STAT1-dependent and STAT1-independent manner, respectively. Similarly, genes recognized as TNF-regulated were clearly distinguishable between RA and SLE patients. While the activity of SLE monocytes was mainly driven by IFN, the activity from RA monocytes showed a dominance of TNF that was characterized by STAT1 down-regulation. The responses to specific cytokines were revealed to be disease-dependent and reflected the interplay of cytokines within various inflammatory milieus. This study has demonstrated that monocytes from RA and SLE patients exhibit disease-specific gene-expression profiles, which can be molecularly dissected when compared to in vitro-generated cytokine signatures. The results suggest that an assessment of cytokine-response status in monocytes may be helpful for improvement of diagnosis and selection of the best cytokine target for therapeutic intervention.
Publication Title
The multifaceted balance of TNF-α and type I/II interferon responses in SLE and RA: how monocytes manage the impact of cytokines.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment, Subject
View Samples- Rattus norvegicus
- 39 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Sustained caloric restriction (CR) extends lifespan in animal models but the mechanism and primary tissue target(s) have not been identified. Gene expression changes with aging and CR were examined in both heart and subcutaneous white adipose tissue (WAT) of F344 male rats using Affymetrix RAE 230 arrays and validated by qRT-PCR on 18 genes. In heart, age- associated changes but not CR-associated changes in old. In WAT, genes were identified where the aging change is suppressed by CR (candidate markers of healthy aging) and those affected by CR but not normal aging (candidate longevity assurance genes). 10-21% of age-associated genes were regulated in common between tissues. Gene set enrichment analysis (GSEA) revealed coordinate small magnitude changes in ribosomal, proteasomal, and mitochondrial genes with similarities between heart and WAT. Further analysis revealed PPARgamma as a potential upstream regulator of altered gene expression in old CR WAT. These results demonstrate a reduced mRNA response to CR with age in heart relative to WAT. In WAT, we identified candidate CR mimetic targets and candidate markers of healthy aging. These data suggest a role for subcutaneous WAT in the effects of CR and strengthen the role for PPAR signaling in aging and CR while indicating that the effects of CR in heart can occur independent of global changes in mRNA level.
Publication Title
Transcriptional response to aging and caloric restriction in heart and adipose tissue.
Sample Metadata Fields
No sample metadata fields
View Samples- Oryza sativa indica group
- 10 Downloadable Samples
- Affymetrix Rice Genome Array (rice)
Description
Rice transgenic plants of the bZIP encoding gene, OsbZIP48, in the Pusa Basmati 1 (PB1) variety have been found to display differences in the total height. In order to elucidate changes at the transcriptome level, microarray of the 10-day-old seedlings of over-expresseion (OE) and knock-down (KD) lines along with vector control (VC) were carried out.
Publication Title
OsbZIP48, a HY5 Transcription Factor Ortholog, Exerts Pleiotropic Effects in Light-Regulated Development.
Sample Metadata Fields
Age, Specimen part
View Samples- Danio rerio
- 5 Downloadable Samples
- Zebrafish Gene 1.0 ST Array (zebgene10st)
Description
drl expression initiates during gastrulation and condenses as a band of cells at the prospective lateral embryo margin. In late epiboly, drl:EGFP is detectable as a band of scattered EGFP-fluorescent cells; after gastrulation, drl:EGFP-positive cells coalesce at the embryo margin that then in somitogenesis break down into the anterior and posterior lateral plate with subsequent cell migrations that form the posterior vascular/hematopoietic stripes and the anterior cardiovascular and myeloid precursors.
Publication Title
Chamber identity programs drive early functional partitioning of the heart.
Sample Metadata Fields
Age, Specimen part
View Samples- Drosophila melanogaster
- 11 Downloadable Samples
Illumina HiSeq 2000, Illumina HiSeq 2500
Description
We report the application of ultrashort metabolic labeling of RNA for high-throughput profiling of RNA processing in Drosophila S2 cells. Overall design: Examination of 3 different labeling timepoints in Drosophila S2 cells.
Publication Title
The kinetics of pre-mRNA splicing in the <i>Drosophila</i> genome and the influence of gene architecture.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 20 Downloadable Samples
- Illumina HiSeq 2000
Description
Alas2 gene encodes the rate-limiting enzyme in heme biosynthesis. CRISPR/Cas9-mediated ablation of two Alas2 intronic cis-elements strongly reduced GATA-1-induced Alas2 transcription, heme biosynthesis, and GATA-1 regulation of other vital constituents of the erythroid cell transcriptome. Bypassing Alas2 function in Alas2 cis-element-mutant (double mutant) cells by providing its catalytic product 5-aminolevulinic acid (5-ALA) rescued heme biosynthesis and the GATA-1-dependent genetic network. We discovered a GATA factor- and heme-dependent circuit that establishes the erythroid cell transcriptome. Overall design: G1E-ER-GATA-1 WT and double mutant cells were examined. Untreated WT, beta-estradiol-treated WT, beta-estradiol-treated double-mutant, and beta-estradiol/5-ALA-treated double-mutant cells were subjected to RNA-seq.
Publication Title
Mechanism governing heme synthesis reveals a GATA factor/heme circuit that controls differentiation.
Sample Metadata Fields
Treatment, Subject
View Samples- Homo sapiens
- 11 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Using Affymetrix microarray technology we analyzed the gene expression profiles of the most important pathological categories of bladder cancer in order to detect potential marker genes. Applying an unsupervised cluster algorithm we observed clear differences between tumor and control samples, as well as between superficial and muscle invasive tumors. According to cluster results, the T1 high grade tumor type presented a global genetic profile which could not be distinguished from invasive cases. We described a new measure to classify differentially expressed genes and we compared it against the B-rank statistic as a standard method. According to this new classification method, the biological functions overrepresented in top differentially expressed genes when comparing tumor versus control samples were associated with growth, differentiation, immune system response, communication, cellular matrix and enzyme regulation. Comparing superficial versus invasive samples, the most important overrepresented biological category was growth and, specifically, DNA synthesis and mitotic cytoskeleton. On the other hand, some under expressed genes have been clearly related to muscular tissue contamination in control samples. Finally, we demonstrated that a pool strategy could be a good option to detect the best differentially expressed genes between two compared conditions.
Publication Title
DNA microarray expression profiling of bladder cancer allows identification of noninvasive diagnostic markers.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Transient over-expression of defined combinations of master regulator genes can effectively induce cellular reprogramming: the acquisition of an alternative predicted phenotype from a differentiated cell lineage. This can be of particular importance in cardiac regenerative medicine wherein the heart lacks the capacity to heal itself, but simultaneously contains a large pool of fibroblasts. In this study we determined the cardio-inducing capacity of ten transcription factors to actuate cellular reprogramming of mouse embryonic fibroblasts into cardiomyocyte-like cells. Over-expression of transcription factors MYOCD and SRF alone or in conjunction with Mesp1 and SMARCD3 significantly enhanced the basal but necessary cardio-inducing effect of the previously reported GATA4, TBX5, and MEF2C. In particular, combinations of five or seven transcription factors significantly enhanced the activation of cardiac reporter vectors, and induced an upregulation of cardiac-specific genes. Global gene expression analysis also demonstrated a significantly greater cardio-inducing effect when the transcription factors MYOCD and SRF were used. Detection of cross-striated cells was highly dependent on the cell culture conditions and was enhanced by the addition of valproic acid and JAK inhibitor. Although we detected Ca2+ transient oscillations in the reprogrammed cells, we did not detect significant changes in resting membrane potential or spontaneously contracting cells. This study further elucidates the cardio-inducing effect of the transcriptional networks involved in cardiac cellular reprogramming, contributing to the ongoing rational design of a robust protocol required for cardiac regenerative therapies.
Publication Title
Transcription factors MYOCD, SRF, Mesp1 and SMARCD3 enhance the cardio-inducing effect of GATA4, TBX5, and MEF2C during direct cellular reprogramming.
Sample Metadata Fields
Specimen part
View Samples