APRIL (TNFSF13) is a ligand of the TNF superfamily which binds to two receptors, BCMA and TACI. We have found that APRIL and its receptor BCMA are specifically enhanced in hepatocellular carcinoma, as compared to non-cancerous liver tissue. We further identified that HepG2 cells present the same ligand/receptor pattern as human hepatocellular carcinomas. We investigated the role of APRIL in HepG2 gene expression in a time course study.
APRIL binding to BCMA activates a JNK2-FOXO3-GADD45 pathway and induces a G2/M cell growth arrest in liver cells.
Specimen part, Cell line
View SamplesNormal children, children with SIRS, children with sepsis, and children with septic shock.
Genomic expression profiling across the pediatric systemic inflammatory response syndrome, sepsis, and septic shock spectrum.
No sample metadata fields
View SamplesVoluntary exercise reduces the risk of cancer and lowers the risk of disease recurrence. Yet the mechanisms for this protection remain to be elucidated. Here we demonstrate that exercise halves tumor growth through an exercise-dependent mobilization and intratumoral infiltration of NK cells in malignant melanoma. Using voluntary wheel running, we show that exercise prior to and during B16 tumor challenge reduced tumor growth by 67%, and this reduction was associated with increased inflammation and immune cell infiltrates, especially NK cells, in the tumors from exercising mice. Depletion of NK cells blunted the exercise-dependent reduction in tumor growth. Moreover, during exercise, NK cells were engaged through an epinephrine-dependent mobilization to the circulation and redistributed to peripheral tissues through an IL-6 dependent mechanism. This study highlights the importance of exercise-dependent immune regulation in the control of malignant melanoma
Voluntary Running Suppresses Tumor Growth through Epinephrine- and IL-6-Dependent NK Cell Mobilization and Redistribution.
Sex, Specimen part
View SamplesRationale: We previously generated genome-wide expression data in children with septic shock, based on whole blood-derive RNA, having the potential to lead the field into novel areas of investigation.
Validating the genomic signature of pediatric septic shock.
Sex
View SamplesSkeletal muscle is one of the primary tissues involved in the development of type 2 diabetes (T2D). Obesity is tightly associated with T2D, making it challenging to isolate specific effects attributed to the disease alone. By using an in vitro myocyte model system we were able to isolate the inherent properties retained in myocytes originating from donor muscle precursor cells, without being confounded by varying extracellular factors present in the in vivo environment of the donor. We generated and characterized transcriptional profiles of myocytes from 24 human subjects, using a factorial design with two levels each of the factors T2D (healthy or diseased) and obesity (non-obese or obese), and determined the influence of each specific factor on genome-wide transcription. We identified a striking similarity of the transcriptional profiles associated independently with T2D or obesity. Obesity thus presents an inherent phenotype in skeletal myocytes, similar to that induced by T2D. Through bioinformatics analysis we found a candidate epigenetic mechanism, H3K27me3 histone methylation, mediating the observed transcriptional signatures. Functional characterization of the expression profiles revealed dysregulated myogenesis and down-regulated muscle function in connection with T2D and obesity, as well as up-regulation of genes involved in inflammation and the extracellular matrix. Further on, we identified a metabolite subnetwork involved in sphingolipid metabolism and affected by transcriptional up-regulation in T2D. Collectively, these findings pinpoint transcriptional changes that are hard-wired in skeletal myocytes in connection with both obesity and T2D. Overall design: Isolated skeletal muscle precursor cells from 24 males and females (6 normal glucose tolerant, 6 obese, 6 type 2 diabetic, and 6 obese and type 2 diabetic) were differentiated in vitro and stimulated with insulin. RNA from fully differentiated myotubes sampled at 0, 0.5, 1, and 2 hours after insulin stimulation was quantified using RNA-seq (96 samples in total). The 6 base-line (0h) samples from normal glucose tolerant individuals are available under the submission GSE63887, the remaining 90 samples are contained in this submission.
Type 2 diabetes and obesity induce similar transcriptional reprogramming in human myocytes.
No sample metadata fields
View SamplesSkeletal myocytes are metabolically active and susceptible to insulin resistance, thus implicated in type 2 diabetes (T2D). This complex disease involves systemic metabolic changes and their elucidation at the systems level requires genome-wide data and biological networks. Genome-scale metabolic models (GEMs) provide a network-context to integrate high-throughput data. We generated myocyte-specific RNA-seq data and investigated their correlation with proteome data. These data were then used to reconstruct a comprehensive myocyte GEM. Next, we performed a meta-analysis of six studies comparing muscle transcription in T2D versus healthy subjects. Transcriptional changes were mapped on the myocyte GEM, revealing extensive transcriptional regulation in T2D, particularly around pyruvate oxidation, branched-chain amino acid catabolism, and tetrahydrofolate metabolism, connected through the down-regulated dihydrolipoamide dehydrogenase. Strikingly, the gene signature underlying this metabolic regulation successfully classifies the disease state of individual samples, suggesting that regulation of these pathways is a ubiquitous feature of myocytes in response to T2D. Overall design: Isolated skeletal muscle precursor cells from six normal glucose tolerant and non-obese males and females were differentiated in vitro. RNA from fully differentiated myotubes was sequenced using RNA-seq.
Type 2 diabetes and obesity induce similar transcriptional reprogramming in human myocytes.
No sample metadata fields
View SamplesThis experiment aimed to investigate whether cells that express the L-Lysine-producing enzyme lyr exhibit any mRNA changes when grown on precursor D-Lysine relative to L-Lysine.
Cell-selective labeling using amino acid precursors for proteomic studies of multicellular environments.
Cell line
View SamplesThis experiment aimed to investigate whether cells that express the L-Lysine-producing enzyme DDC exhibit any mRNA changes when grown on precursor DAP relative to L-Lysine.
Cell-selective labeling using amino acid precursors for proteomic studies of multicellular environments.
Cell line
View SamplesGoal of the experiment: To identify correlated genes, pathways and groups of patients with systemic inflammatory response syndrome and septic shock that is indicative of biologically important processes active in these patients.
Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genome-wide profiling identifies a DNA methylation signature that associates with TET2 mutations in diffuse large B-cell lymphoma.
Specimen part
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