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GSE46970
Mus musculus
15 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
In order to identify genes that are activated in differentiating WT ESCs, but are missing in Tal-1-/- and Runx1-/- ESCs, and which might be involved in the generation of definitive hematopoietic progenitors and their specification thereafter, we performed microarray analyses on purified Flk-1+ cells, differentiated from these ESCs for 4, 5, and 6 days in vitro.
Publication Title
Ectopic Runx1 expression rescues Tal-1-deficiency in the generation of primitive and definitive hematopoiesis.
Sample Metadata Fields
Specimen part, Cell line, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Recent data from our group, demonstrate that infusion of myelin oligodendrocyte glycoprotein (MOG35-55) peptide, leads to induction of MOG35-55-specific Tregs and subsequent suppression of Experimental Autoimmune Encephalomyelitis (EAE), the mouse model of multiple sclerosis. Amelioration of EAE was accompanied by reduced MOG-specific Th1 and Th17 responses in the draining lymph nodes (dLNs). Phenotypic analysis of the dLNs of MOG-infused mice revealed a significant Treg-mediated reduction in the recruitment of 7AAD-CD3-CD19-CD11c+CD11bhighGr-1+ iDCs compared to non-infused control immunized mice. Focusing on the delineation of novel molecules/genes that are involved in the MOG-specific Treg-mediated suppression of autoimmune responses, we have isolated highly purified iDCs from MOG infused and non-infused control immunized mice.
Publication Title
De novo-induced self-antigen-specific Foxp3+ regulatory T cells impair the accumulation of inflammatory dendritic cells in draining lymph nodes.
Sample Metadata Fields
Sex, Specimen part
View Samples- 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
- 26 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This study demonstrates quantitative and qualitative differences between type I IFN signatures in autoimmunity and viral infection using purified CD4pos T cells and CD16pos- and CD16neg-monocyte subsets. We were able to discriminate between cell-specific viral response signatures and the pathogenically amplified IFN signatures observed in autoimmunity. The differences were of both a qualitative and quantitative nature, as the signatures in the patients with SLE were characterized by much more complexly compiled gene patterns with increased absolute gene expression levels.
Publication Title
Cell-specific type I IFN signatures in autoimmunity and viral infection: what makes the difference?
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- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
To understand differences in the pathogenesis of synovial hyperplasia during TNF-induced arthritis, we compared the global gene expression of hTNFtg and hTNFtg;Rsk2-/y primary synovial fibroblasts.
Publication Title
Rsk2 controls synovial fibroblast hyperplasia and the course of arthritis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Abnormal mitochondria metabolism and innate immune responses participate in the pathogenesis of many inflammatory disorders. The molecular events regulating mitochondrial activity to control survival and cell death in monocytes/macrophages are poorly understood. Here we show that miR-125b attenuates the activity of the mitochondrial respiratory chain through BIK silencing, and promotes the elongation of mitochondrial network through MTP18 targeting, without impacting autophagy, in the human monocytes. Proinflammatory activation is associated with a concomitant increase in miR-125b expression, decrease in BIK and MTP-18 expression, reduced oxidative phosphorylation, and enhanced mitochondrial fusion. Furthermore, expression of M1-associated transcripts as well as mitochondrial dynamics and energy metabolism are induced upon ectopic expression of miR-125b. In turn, by repressing miR-125b, mitochondrial dynamics was preserved, LPS-induced repression of BIK expression and of mitochondrial respiration were prevented, and M1 polarization of macrophages was inhibited. Altogether, our data reveal a novel role for miR-125b in controlling mitochondrial metabolism and dynamics by targeting BIK and MTP18, respectively, two novel cellular target proteins involved in maintaining the mitochondrial integrity in human monocytes. These findings not only suggest a novel function for miR-125b in regulating metabolic adaptation of monocytes to inflammation but also unravel new molecular mechanisms for its pro-apoptotic role and identify potential targets for interfering with inflammatory activation of monocytes.
Publication Title
miR-125b controls monocyte adaptation to inflammation through mitochondrial metabolism and dynamics.
Sample Metadata Fields
Specimen part, Cell line
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- Mus musculus
- 19 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Murine B cells can be activated via the surface receptors TLR4 and CD40. For a global assessment of differences in gene expression between these two different modes of B cell activation a genome wide transcriptome analysis was performed. In order to dissect different gene expression profiles of B cells, activation was induced by LPS or LPS + anti-CD40 for 24h and 72h. Both activation states were compared to each other but also to nave B cells.
Publication Title
IL-35-producing B cells are critical regulators of immunity during autoimmune and infectious diseases.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 43 Downloadable Samples
NextSeq 500
Description
Resistance to platinum-based chemotherapy is a clinical challenge in the treatment of ovarian cancer (OC) and limits survival. Therefore, innovative drugs against platinum-resistance are urgently needed. Our therapeutic concept is based on the conjugation of two chemotherapeutic compounds to a monotherapeutic pro-drug, which is taken up by cancer cells and cleaved into active cytostatic metabolites. Here, we explore the activity of the duplex-prodrug 5-FdU-ECyd, covalently linking 2''-deoxy-5-fluorouridine (5-FdU) and 3''-C-ethynylcytidine (ECyd), on platinum-resistant OC cells. RNA-Sequencing was used for characterization of 5-FdU-ECyd treated platinum-sensitive A2780 and isogenic platinum-resistant A2780cis. Overall design: Platinum-sensitive A2780 and platinum resistant-cells A2780cis were treated with 5-FdU-Ecyd for 6h and 12h, there are also 6h and 12h untreated controls, all groups are in triplicates
Publication Title
The conjugated antimetabolite 5-FdU-ECyd and its cellular and molecular effects on platinum-sensitive vs. -resistant ovarian cancer cells <i>in vitro</i>.
Sample Metadata Fields
Cell line, Subject, Time
View Samples