In this study, mRNA expression profiles of 113 primary untreated human neuroblastoma samples were compared with the aim to identify prognostic exon and gene sets as well as parameters associated with alternative exon use. The primary neuroblastoma specimens were from tumor banks in Cologne or Essen, Germany, Ghent, Belgium and Valencia, Spain. All patients were diagnosed between 1998 and 2007 and treated according to the German Neuroblastoma trials NB97, NB 2004 or the SIOPEN protocol.
Smac mimetic LBW242 sensitizes XIAP-overexpressing neuroblastoma cells for TNF-α-independent apoptosis.
Specimen part, Treatment
View SamplesAnalysis of white adipose tissue of PPARb/d knockout mice. Data may point towards putative target genes of PPARb/d and thus the function of PPARb/d in white adipose tissue. Datasets were used to identify glycogen synthase 2 as novel PPAR target.
Glycogen synthase 2 is a novel target gene of peroxisome proliferator-activated receptors.
Sex, Age, Specimen part
View SamplesClinical remission is apparent when laboratory markers of inflammation are normal and clinical symptoms are absent. However, sub-clinical inflammation can still be present. A detailed analysis of the immune status during this inactive state of disease may provide a useful tool to subcategorize patients with subclinical immune activation
Gene expression analysis of peripheral cells for subclassification of pediatric inflammatory bowel disease in remission.
Specimen part
View SamplesThe objective of this study was the assessment of transcriptional dysregulation in particular with regard to B-cell differentiation factors. Most studies focus on cross-section analyses of various leukemia subtypes to identify differentially regulated genes lacking suitable reference models. Here we applied comparative intraindividual transcriptome analysis of B-precursor ALL of childhood, which introduces a side-by-side analysis of leukemic cells and matched normal lymphoblasts from the same individual in complete continuous remission after the end of re-induction therapy. This approach reduces noise by eliminating interindividual variability.
Aberrant ZNF423 impedes B cell differentiation and is linked to adverse outcome of ETV6-RUNX1 negative B precursor acute lymphoblastic leukemia.
Specimen part, Subject
View SamplesAnalysis of cardiomyocytes cultivated in 2D or age-matched 3D (Engineered heart tissue, EHT) format.
Human Engineered Heart Tissue: Analysis of Contractile Force.
Age, Specimen part
View SamplesInfections of the udder by Escherichia coli very often elicit acute inflammation, while Staphylococcus aureus infections tend to cause mild, subclinical inflammation and persistent infections. The molecular causes undercovering the different disease patterns are poorly understood. We therefore profiled kinetics and extent of global changes in the transcriptome of primary bovine mammary epithelia cells (MEC) subsequent to challenging them with heat inactivated preparations of E. coli or S. aureus pathogens. E. coli swiftly and strongly induced expression of cytokines and bactericidal factors. S. aureus elicited a retarded response and failed to quickly induce expression of bactericidal factors. Both pathogens induced a similar pattern of chemokines for cell recruitment into the udder, but E. coli stimulated their synthesis much faster and stronger. The genes which are exclusively and most strongly up-regulated by E. coli may be clustered into a regulatory network with Tumor necrosis factor alpha (TNF-a) and Interleukin 1 (IL-1) in a central position. In contrast, the expression of these master cytokines is barely regulated by S. aureus. Both pathogens quickly trigger enhanced expression of IL-6. This is still possible after completely abrogating MyD88 dependent TLR-signalling in MEC. The E. coli specific strong induction of TNF-a and IL-1 expression may be causative for the severe inflammatory symptoms of animals suffering from E. coli mastitis while avoidance to quickly induce synthesis of bactericidal factors may support persistent survival of S. aureus within the udder. We suggest that S. aureus subverts MyD88-dependent activation of immune gene expression in MEC.
Comparative kinetics of Escherichia coli- and Staphylococcus aureus-specific activation of key immune pathways in mammary epithelial cells demonstrates that S. aureus elicits a delayed response dominated by interleukin-6 (IL-6) but not by IL-1A or tumor necrosis factor alpha.
Specimen part, Treatment, Time
View SamplesChildhood acute lymphoblastic leukemia (ALL) comprises a large group of genetic subtypes with a favorable prognosis characterized by a TEL-AML1-fusion, hyperdiploidy (>50 chromosomes) or E2A-PBX1 fusion and a smaller group with unfavorable outcome characterized by either a BCR-ABL-fusion, MLL-rearrangement or T-ALL.
A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study.
No sample metadata fields
View SamplesChildhood acute lymphoblastic leukemia (ALL) comprises a large group of genetic subtypes with a favorable prognosis characterized by a TEL-AML1-fusion, hyperdiploidy (>50 chromosomes) or E2A-PBX1 fusion and a smaller group with unfavorable outcome characterized by either a BCR-ABL-fusion, MLL-rearrangement or T-ALL.
A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study.
No sample metadata fields
View SamplesBiologic markers of immune tolerance may facilitate tailoring of immune suppression duration after allogeneic hematopoietic cell transplantation (HCT). In a cross-sectional study, peripheral blood samples were obtained from tolerant (n=15, median 38.5 months post-HCT) and non-tolerant (n=17, median 39.5 post-HCT) HCT recipients and healthy control subjects (n=10) for analysis of immune cell subsets and differential gene expression. There were no significant differences in immune subsets across groups. We identified 281 probe sets unique to the tolerant (TOL) group and 122 for non-tolerant (non-TOL). These were enriched for process networks including NK cell cytotoxicity, antigen presentation, lymphocyte proliferation, and cell cycle and apoptosis. Differential gene expression was enriched for CD56, CD66, and CD14 human lineage-specific gene expression. Differential expression of 20 probe sets between groups was sufficient to develop a classifier with > 90% accuracy, correctly classifying 14/15 TOL cases and 15/17 non-TOL cases. These data suggest that differential gene expression can be utilized to accurately classify tolerant patients following HCT. Prospective investigation of immune tolerance biologic markers is warranted.
Tolerance associated gene expression following allogeneic hematopoietic cell transplantation.
Specimen part, Subject
View SamplesIn this study, we set out to identify those molecular features of the POU transcription factor Oct4 that are responsible for inducing pluripotency in somatic cells. Oct4 is known to have a strong preference to cooperate with Sox2 on heterodimeric SoxOct elements predominantly found in enhancers of genes expressed in embryonic stem cells (ESCs). To test whether this partnership is specific to Oct4, we compared its DNA recognition and reprogramming activities to the paralogous transcription factor Oct6, which cannot induce and maintain pluripotency in mouse cells. By analyzing ChIP-Seq data and performing quantitative dimerization assays, we found that in somatic cells, instead of heterodimerzing with Sox-factors, Oct6 more potently homodimerizes on OctOct elements. We identified that a single amino acid is crucial in directing binding to the respective composite DNA element. As a consequence, just changing this one amino acid hampers Oct4 in generating induced pluripotent stem cells (iPSCs). In contrast, the reverse mutation in Oct6 did not augment its reprogramming activity. This was achieved with at least two additional exchanges. In summary, we demonstrate that cell-type specific POU factor function is determined by a limited set of residues that affect DNA and partner factor interactions. Such relatively minor changes lead to a pronounced impact on regulatory function and reprogramming activity.
Changing POU dimerization preferences converts Oct6 into a pluripotency inducer.
No sample metadata fields
View Samples