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GSE74297
Homo sapiens
3 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
The protease activity of the paracaspase MALT1 plays an important role in antigen receptor-mediated lymphocyte activation by controlling the activity of the transcription factor NF-kB and is thus essential for the expression of inflammatory target genes.
Publication Title
MALT1 Protease Activity Controls the Expression of Inflammatory Genes in Keratinocytes upon Zymosan Stimulation.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 27 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
Diffuse large B-cell lymphoma (DLBCL) represents the most common form of lymphoma. We could show that in DLBCL cell lines the transcription factor NFAT is constitutively activated and drives the survival of a DLBCL subset. Aim of the analysis was to identify NFAT target genes in a NFAT-dependent (HBL-1) or -independent (HT) DLBCL cell line. To block NFAT activity, the DLBCL cells were treated with the calcineurin inhibitor cyclosporin A (CsA) up to 48 h. With this approach, we identified several survival-related NFAT target genes in HBL-1 cells that might explain the toxic effects of calcineurin inhibitors.
Publication Title
Targeting chronic NFAT activation with calcineurin inhibitors in diffuse large B-cell lymphoma.
Sample Metadata Fields
Treatment
View Samples- Homo sapiens
- 133 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Obesity accelerates epigenetic aging of human liver.
Sample Metadata Fields
Sex, Age, Disease, Subject
View Samples- Homo sapiens
- 133 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
N=134 human liver samples from morbidly obese patients and healthy controls were analysed by array-based mRNA expression profiling. Liver messenger RNA expression datasets from the German patients were generated on the HuGene 1.1 ST gene array The purpose of the study was to correlate these gene expression data with body mass index and with an epigenetic measure of age acceleration based on DNA methylation data.
Publication Title
Obesity accelerates epigenetic aging of human liver.
Sample Metadata Fields
Sex, Age, Disease, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Interference with chemoresistance to enhance the efficacy of chemotherapeutics may be of great utility for cancer therapy. We have identified KINK-1 (Kinase Inhibitor of NF-kappaB-1), a highly selective small-molecule IKKkappa inhibitor, as a potent suppressor of both constitutive and induced NF-kappaB activity in melanoma cells. While KINK-1 profoundly diminished various NF-kappaB-dependent gene products regulating proliferation, cytokine production or anti-apoptotic responses, the compound by itself showed little antiproliferative or pro-apoptotic activity on the cellular level. However, its combination with some cytostatics markedly enhanced their antitumoral activities in vitro, and doxorubicin-induced NF-kappaB activation, a mechanism implicated in chemoresistance, was abrogated by KINK-1. In addition, when KINK-1 was combined with doxorubicin in an in vivo melanoma model, experimental metastasis was significantly diminished as compared to either treatment alone. Induction of chemoresistance by KINK-1 in vivo was not observed. Thus, KINK-1 or related substances might increase the susceptibility of tumors to chemotherapy.
Publication Title
KINK-1, a novel small-molecule inhibitor of IKKbeta, and the susceptibility of melanoma cells to antitumoral treatment.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 72 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in industrialized countries. Liver samples from morbidly obese patients (N=45) with all stages of NAFLD and controls (N=18) were analysed by array-based DNA methylation and mRNA expression profiling. NAFLD-specific expression and methylation differences were seen for nine genes coding for key enzymes in intermediate metabolism (including PC, ACLY, PLCG1) and insulin/insulin-like signalling (including IGF1, IGFBP2, PRKCE) and replicated by bisulfite pyrosequening (independent N=39). Transcription factor binding sites at NAFLD-specific CpG sites were >1000-fold enriched for ZNF274, PGC1A and SREBP2. Intra-individual comparison of liver biopsies before and after bariatric surgery showed NAFLD-associated methylation changes to be partially reversible. Post-bariatric and NAFLD-specific methylation signatures were clearly distinct both in gene-ontology and transcription factor binding site analyses, with >400-fold enrichment of NRF1, HSF1 and ESRRA sites. Our findings provide one of the first examples of treatment-induced epigenetic organ remodelling in humans.
Publication Title
DNA methylation analysis in nonalcoholic fatty liver disease suggests distinct disease-specific and remodeling signatures after bariatric surgery.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 83 Downloadable Samples
Illumina HiScanSQ
Description
In this study we investigated the effect of normal chow (0 % cholesterol) or a semisynthetic diet (high sugar, 0.02 % cholesterol) fed to mice lacking either Mc4r, Ldlr or both and wildtype animals (total of 4 genotypes) by generating an expression profile of their livers after 6 months by RNA sequencing. Overall design: We investigated mice lacking either Mc4r, Ldlr or both and wildtype animals fed with normal chow or a semisynthetic diet with 10 replicates for each of the 8 resulting groups (4 genotypes * 2 diets).
Publication Title
Severe Atherosclerosis and Hypercholesterolemia in Mice Lacking Both the Melanocortin Type 4 Receptor and Low Density Lipoprotein Receptor.
Sample Metadata Fields
Age, Specimen part, Cell line, Subject
View Samples- Mus musculus
- 29 Downloadable Samples
- Illumina HiScanSQ, Illumina HiSeq 2500
Description
Naive spleens as well as naive and LPS-treated dendritic cells from wildtype and GPR34-/- mice were sequenced to integrate expression profiles with protein interaction networks and find functional modules that are affected by GPR34 Overall design: Expression profiles of dendritic cells and whole spleens were generated using Illumina HiSeq 2500/ Illumina HiScan
Publication Title
Dendritic Cells Regulate GPR34 through Mitogenic Signals and Undergo Apoptosis in Its Absence.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 22 Downloadable Samples
- Sentrix Human-6 Expression BeadChip
Description
Regulatory T (Treg) cells are involved in self tolerance, immune homeostasis, prevention of autoimmunity, and suppression of immunity to pathogens or tumours. The forkhead transcription factor FOXP3 is essential for Treg cell development and function as mutations in FOXP3 cause severe autoimmunity in mice and humans. However, the FOXP3-dependent molecular mechanisms leading to this severe phenotype are not well understood. Here we introduce the chromatin remodelling enzyme SATB1 (special AT-rich sequence-binding protein-1) as an important target gene of FOXP3. So far, SATB1 has been associated with normal thymic T-cell development, peripheral T-cell homeostasis, TH1/TH2 polarization, and reprogramming of gene expression. In natural and induced murine and human FOXP3+ Treg cells SATB1 expression is significantly reduced. While there is no differential epigenetic regulation of the SATB1 locus between Treg and Teffector cells, FOXP3 reduces SATB1 expression directly as a transcriptional repressor at the SATB1 locus and indirectly via miR-155 induction, which specifically binds to the 3UTR of the SATB1 mRNA. Reduced SATB1 expression in FOXP3+ cells achieved either by overexpression or induction of FOXP3 is linked to significant reduction in TH1 and TH2 cytokines, while loss of FOXP3 function either by knock down or genetic mutation leads to significant upregulation of SATB1 and subsequent cytokine production. Alltogether, these findings demonstrate that reduced SATB1 expression in Treg cells is necessary for maintenance of a Treg-cell phenotype in vitro and in vivo and places SATB1-mediated T cell-specific modulation of global chromatin remodelling central during the decision process between effector and regulatory T-cell function.
Publication Title
Repression of the genome organizer SATB1 in regulatory T cells is required for suppressive function and inhibition of effector differentiation.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Treatment
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mucolipidosis type II (MLII) is a severe inherited multisystemic disorder caused by mutations in the GNPTAB gene. Skeletal abnormalities are a predominant feature of MLII. Here we investigate the gene expression in a knock-in mouse model for mucolipidosis type II, generated by the insertion of a cytosine in the murine Gnptab gene (c.3082insC) that is homologous to a homozygous mutation in an MLII patient.
Publication Title
Decreased bone formation and increased osteoclastogenesis cause bone loss in mucolipidosis II.
Sample Metadata Fields
Specimen part
View Samples