In mammals, expansion of adipose tissue mass induces accumulation of adipose tissue macrophages (ATMs). We isolated CD11c- (FB) and CD11c+ (FBC) perigonadal ATMs from SVCs of lean (C57BL/6J Lep +/+) and obese leptin-deficient (C57BL/6J Lep ob/ob) mice.
Obesity activates a program of lysosomal-dependent lipid metabolism in adipose tissue macrophages independently of classic activation.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Reverse engineering a hierarchical regulatory network downstream of oncogenic KRAS.
Cell line, Treatment
View SamplesRAS mutations are highly relevant for progression and therapy response of human tumours, but the genetic network that ultimately executes the oncogenic effects is poorly understood. Here we used a reverse-engineering approach in an ovarian cancer model to reconstruct KRAS oncogene-dependent cytoplasmic and transcriptional networks from perturbation experiments based on gene silencing and pathway inhibitor treatments. We measured mRNA and protein levels in manipulated cells by microarray, RT-PCR and Western Blot analysis, respectively. The reconstructed model revealed complex interactions among the transcriptional and cytoplasmic components, some of which were confirmed by double pertubation experiments. Interestingly, the transcription factors decomposed into two hierarchically arranged groups. To validate the model predictions we analysed growth parameters and transcriptional deregulation in the KRAS-transformed epithelial cells. As predicted by the model, we found two functional groups among the selected transcription factors. The experiments thus confirmed the predicted hierarchical transcription factor regulation and showed that the hierarchy manifests itself in downstream gene expression patterns and phenotype.
Reverse engineering a hierarchical regulatory network downstream of oncogenic KRAS.
Cell line, Treatment
View SamplesLactoferrin is a highly multifunctional protein. Indeed, it is involved in many physiological functions, including regulation of iron absorption and immune responses.
A nutritional supplement containing lactoferrin stimulates the immune system, extends lifespan, and reduces amyloid <i>β</i> peptide toxicity in <i>Caenorhabditis elegans</i>.
No sample metadata fields
View SamplesRAS mutations are highly relevant for progression and therapy response of human tumours, but the genetic network that ultimately executes the oncogenic effects is poorly understood. Here we used a reverse-engineering approach in an ovarian cancer model to reconstruct KRAS oncogene-dependent cytoplasmic and transcriptional networks from perturbation experiments based on gene silencing and pathway inhibitor treatments. We measured mRNA and protein levels in manipulated cells by microarray, RT-PCR and Western Blot analysis, respectively. The reconstructed model revealed complex interactions among the transcriptional and cytoplasmic components, some of which were confirmed by double pertubation experiments. Interestingly, the transcription factors decomposed into two hierarchically arranged groups. To validate the model predictions we analysed growth parameters and transcriptional deregulation in the KRAS-transformed epithelial cells. As predicted by the model, we found two functional groups among the selected transcription factors. The experiments thus confirmed the predicted hierarchical transcription factor regulation and showed that the hierarchy manifests itself in downstream gene expression patterns and phenotype.
Reverse engineering a hierarchical regulatory network downstream of oncogenic KRAS.
Cell line, Treatment
View SamplesIn osteosarcoma patients, the development of metastases, often to the lungs, is the most frequent cause of death. To improve this situation, a deeper understanding of the molecular mechanisms governing osteosarcoma development and dissemination and the identification of novel drug targets for an improved treatment are needed. Towards this aim, we characterized osteosarcoma tissue samples compared to primary osteoblast cells using Affymetrix HG U133A microarrays.
De novo expression of EphA2 in osteosarcoma modulates activation of the mitogenic signalling pathway.
No sample metadata fields
View SamplesGoals of the study was to compare transcripional and phenotypic response of mouse intestinal organoid cultures to the PIK3CA(H1047R) and CTNNB1(stab) oncogenes. Overall design: Two biological replicates of organoids with transgenic tdTomato-Luciferase, tdTomato-PIK3CAH1047R, tdTomato-CTNNB1stab or td-Tomato-PIK3CAH1047R-CTNNB1stab were analysed by RNA-Seq By comparing 7-10 x 10E7 50bp paired end reads per library we identify transcriptional alterations in the intestinal epithelium following expression of each or both oncogenes,
Oncogenic β-catenin and PIK3CA instruct network states and cancer phenotypes in intestinal organoids.
Specimen part, Cell line, Subject
View SamplesTo investigate potential differences between strong and weak oscillators at the gene expression level we carried out a transcriptome analysis for each cell line. Our results indicate that phenotypic circadian clock differences are reflected by gene expression differences both in genes of the core network, but also in additional genes not directly associated with circadian clock functions.
Ras-mediated deregulation of the circadian clock in cancer.
Specimen part, Cell line, Time
View SamplesPatients had low calorie diet weight reduction run in prior to the day of surgery. The human liver and subcutaneous fat tissue samples were obtained from 12 obese subjects undergoing bariatric surgery and then used for the mRNA expression analyses. Overall design: mRNA profiles of human liver and subcutaneous fat tissue samples were generated by RNA sequencing using Illumina HiSeq 2500.
Integrated Network Analysis Reveals an Association between Plasma Mannose Levels and Insulin Resistance.
Age, Specimen part, Subject
View SamplesGoals of the study was to compare transcripional and phenotypic response of mouse intestinal organoid cultures to the KRAS(G12V) or BRAF(V600E)oncogenes. Overall design: Two biological replicates of organoids with transgenic luc-tdTomato, KRAS(G12V)-tdTomato, BRAF(V600E)-tdTomato were analysed by RNA-Seq By comparing 7-10 x 10E7 50bp paired end reads per library we identify transcriptional alterations in the intestinal epithelium following expression of each oncogene
Cell type-dependent differential activation of ERK by oncogenic KRAS in colon cancer and intestinal epithelium.
Specimen part, Cell line, Subject
View Samples