Retinol Saturase (RetSat) is an oxidoreductase expressed at high levels in the hepatocyte fraction of liver.
Retinol saturase coordinates liver metabolism by regulating ChREBP activity.
No sample metadata fields
View SamplesInsulin degrading enzyme (IDE) is a major enzyme responsible for insulin degradation in the liver. The modulation of insulin degrading enzyme activity is hypothesized to be a link between T2DM and liver cancer. Results provide insight into role of IDE in proliferation and other cell functions.
Modulation of insulin degrading enzyme activity and liver cell proliferation.
Cell line
View SamplesGene expression profiling revealed over-representation of a distinct (proneural-like) expression signature in long-term survivors that was linked to IDH1/2 mutation. However, among the IDH1/2-wildtype patients, tumors from long-term survivors did not show distinct gene expression profiles and included proneural, classical and mesenchymal glioblastoma subtypes.
Molecular characterization of long-term survivors of glioblastoma using genome- and transcriptome-wide profiling.
Specimen part
View SamplesMolecular profiling of cerebral gliomas distinguishes biologically distinct tumor groups and provides prognostically relevant information beyond histological classification and IDH1/2 mutation status.
Molecular classification of diffuse cerebral WHO grade II/III gliomas using genome- and transcriptome-wide profiling improves stratification of prognostically distinct patient groups.
Disease
View SamplesRecent technological advances in single-cell genomics make it possible to analyze cellular heterogeneity of tumor samples. Here, we applied single-cell RNA-seq to measure the transcriptomes of 307 single cells cultured from three biopsies of three different patients with a BRAF/NRAS wild type, BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant melanoma metastasis, respectively. Analysis based on self-organizing maps identified sub-populations defined by multiple gene expression modules involved in proliferation, oxidative phosphorylation, pigmentation and cellular stroma. Gene expression modules had prognostic relevance when compared with gene expression data from published melanoma samples and patient survival data. We surveyed kinome expression patterns across sub-populations of the BRAF/NRAS wild type sample and found that CDK4 and CDK2 were consistently highly expressed in the majority of cells, suggesting that these kinases might be involved in melanoma progression. Treatment of cells with the CDK4 inhibitor palbociclib restricted cell proliferation to a similar, and in some cases greater, extent than MAPK inhibitors. Finally, we identified a low abundant sub-population in this sample that highly expressed a module containing ABC transporter ABCB5, surface markers CD271 and CD133, and multiple aldehyde dehydrogenases (ALDHs), as markers for melanoma stem or initiating cells. Patient-derived cultures of the BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant metastases showed more homogeneous single-cell gene expression patterns with gene expression modules for proliferation and ABC transporters. Taken together, our results describe an intertumor and intratumor heterogeneity in melanoma short-term cultures which might be relevant for patient survival, and suggest promising targets for new treatment approaches in melanoma therapy. Overall design: RNA-seq of 307 single cells cultured from three biopsies of three different patients with a BRAF/NRAS wild type, BRAF mutant/NRAS wild type and BRAF wild type/NRAS mutant melanoma metastasis, respectively.
Pseudotime Dynamics in Melanoma Single-Cell Transcriptomes Reveals Different Mechanisms of Tumor Progression.
Specimen part, Subject
View SamplesMicroarray analysis and quantitative real-time PCR revealed that TB40E infection of DCs led to changes of the gene expression pattern. A variety of pro-inflammatory cytokines and chemokines (CXCL10, CXCL11, CCL5), TLR3 and genes whose products function downstream of the TLR3 signalling pathway (e.g. IFN-, IFN-) were significantly upregulated.
Toll-like receptor 3 has no critical role during early immune response of human monocyte-derived dendritic cells after infection with the human cytomegalovirus strain TB40E.
Specimen part
View SamplesDCs are localized under the mucosa of the lungs and the gastrointestinal tract, and therefore come into close contact with A. fumigatus germ tubes during early steps of infection as soon as fungi become invasive. For a more detailed insight into differentially regulated genes, whole genome microarray analysis was performed.
Impact of mycophenolic acid on the functionality of human polymorphonuclear neutrophils and dendritic cells during interaction with Aspergillus fumigatus.
No sample metadata fields
View SamplesIn a whole-transcriptome study, cellular responses of DCs confronted with the fungi A. fumigatus, C. albicans or the bacterial cell wall component LPS were investigated. Therefore DCs of four independent donors were analyzed after 6 hours co-culture with A. fumigatus, C. albicans and LPS by Affymetrix whole genome expression arrays. In general, transcriptomic analysis revealed a clustering of the A. fumigatus and C. albicans stimulated DCs. However, LPS and fungi-dependent gene expression showed more common similarities compared to the untreated control. Stimulation with LPS induced a differential regulation of 2793 genes after 6h, while confrontation with A. fumigatus and C. albicans resulted in 743 and 974 differentially regulated genes, respectively. Kruppel-like factor 4 (KLF4) was identified as the only transcription factor that was down-regulated in DCs by both fungi but induced by stimulation with LPS.
Krüppel-like Factor 4 modulates interleukin-6 release in human dendritic cells after in vitro stimulation with Aspergillus fumigatus and Candida albicans.
Specimen part, Subject
View SamplesMicroarray-based classifiers and prognosis models identify subgroups with distinct clinical outcomes and high risk of AML transformation of myelodysplastic syndrome (MDS)
Microarray-based classifiers and prognosis models identify subgroups with distinct clinical outcomes and high risk of AML transformation of myelodysplastic syndrome.
Disease, Disease stage
View SamplesBased on the assumption that molecular mechanisms involved in cancerogenesis are characterized by groups of coordinately expressed genes, we developed and validated a novel method for analyzing transcriptional data called Correlated Gene Set Analysis (CGSA). Using 50 extracted gene sets we identified three different profiles of tumors in a cohort of 364 Diffuse large B-cell (DLBCL) and related mature aggressive B-cell lymphomas other than Burkitt lymphoma. The first profile had high level of expression of genes related to proliferation whereas the second profile exhibited a stromal and immune response phenotype. These two profiles were characterized by a large scale gene activation affecting genes which were recently shown to be epigenetically regulated, and which were enriched in oxidative phosphorylation, energy metabolism and nucleoside biosynthesis. The third and novel profile showed only low global gene activation similar to that found in normal B cells but not cell lines. Our study indicates novel levels of complexity of DLBCL with low or high large scale gene activation related to metabolism and biosynthesis and, within the group of highly activated DLBCLs, differential behavior leading to either a proliferative or a stromal and immune response phenotype.
Massive transcriptional perturbation in subgroups of diffuse large B-cell lymphomas.
No sample metadata fields
View Samples