In this analysis we have compared the gene expression profiles of lymphatic endothelial cells (LECs) isolated from human intestine (iLECs) versus LECs from human skin (dLECs).
Liprin (beta)1 is highly expressed in lymphatic vasculature and is important for lymphatic vessel integrity.
Specimen part
View SamplesAnorexia can occur as a serious complication of chronic disease. Increasing evidence suggests that inflammation plays a major role, along with a hypothalamic dysregulation characterized by locally elevated serotonin levels. The present study was undertaken to further explore the connections between peripheral inflammation, anorexia and hypothalamic serotonin metabolism and signaling pathways. We studied transcriptomic changes and serotonergic activity in the hypothalamus of mice after an intraperitoneal injection with TNF, IL-6 or a combination of TNF and IL-6.
Increased hypothalamic serotonin turnover in inflammation-induced anorexia.
Sex, Specimen part, Treatment
View SamplesCalorie restriction (CR) has been shown to extend life- and health-span in model species. For most humans, a life-long CR diet is too arduous to adhere to. The aim of this study was to explore whether weekly intermittent CR can 1) provide long-term beneficial effects and 2) counteract diet-induced obesity in male aging mice. In this study, we have exposed C57Bl/6J mice for 24 months to an intermittent (INT) diet, alternating weekly between CR of a control diet and ad libitum moderate-fat (MF) feeding. This weekly intermittent CR significantly counteracted the adverse effects of the MF diet on mortality, body weight and liver health markers in male 24-month-old mice. Hepatic gene expression profiles of INT-exposed animals appeared much more comparable to CR than to MF-exposed mice. At 12 months of age, a subgroup of MF-exposed mice was transferred to the INT diet. Gene expression profiles in the liver of the 24-month-old diet switch mice were highly similar to the INT-exposed mice. However, a small subset of genes was consistently changed by the MF diet during the first phase of life. Weekly intermittent CR largely, but not completely, reversed adverse effects caused by a MF diet.
Intermittent calorie restriction largely counteracts the adverse health effects of a moderate-fat diet in aging C57BL/6J mice.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Hypothalamic food intake regulation in a cancer-cachectic mouse model.
Sex, Specimen part, Treatment
View SamplesAppetite is frequently affected in cancer patients, leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer cachectic mouse model with increased food intake. In this model, mice bearing C26 colon adenocarcinoma have an increased food intake subsequently to the loss of body weight. We hypothesize that in this model, appetite regulating systems in the hypothalamus, which apparently fail in anorexia, are still able to adapt adequately to changes in energy balance. Therefore studying the changes that occur on appetite regulators in the hypothalamus might reveal targets for treatment of cancer-induced eating disorders. By applying transcriptomics, many appetite regulating systems in the hypothalamus could be taken into account, providing an overview of changes that occur in the hypothalamus during tumour growth. We show that hypothalamic expression of orexigenic neuropeptides NPY and AgRP was higher, whereas expression of anorexigenic genes CCK and POMC were lower in TB compared to controls. In addition, serotonin and dopamine signalling pathways were found to be significantly altered in TB mice. Serotonin levels in brain showed to be lower in TB mice compared to control mice, while dopamine levels did not change. Moreover, serotonin levels inversely correlated with food intake. Transcriptomic analysis of the hypothalamus of cachectic TB mice with an increased food intake showed changes in NPY, AgRP and serotonin signalling. Serotonin levels in the brain showed to correlate with changes in food intake. Targeting these systems seems a promising strategy to avoid the development of cancer-induced eating disorders.
Hypothalamic food intake regulation in a cancer-cachectic mouse model.
Sex, Specimen part, Treatment
View SamplesAppetite is frequently affected in cancer patients, leading to anorexia and consequently insufficient food intake. In this study, we report on hypothalamic gene expression profile of a cancer cachectic mouse model with increased food intake. In this model, mice bearing C26 colon adenocarcinoma have an increased food intake subsequently to the loss of body weight. We hypothesize that in this model, appetite regulating systems in the hypothalamus, which apparently fail in anorexia, are still able to adapt adequately to changes in energy balance. Therefore studying the changes that occur on appetite regulators in the hypothalamus might reveal targets for treatment of cancer-induced eating disorders. By applying transcriptomics, many appetite regulating systems in the hypothalamus could be taken into account, providing an overview of changes that occur in the hypothalamus during tumour growth. We show that hypothalamic expression of orexigenic neuropeptides NPY and AgRP was higher, whereas expression of anorexigenic genes CCK and POMC were lower in TB compared to controls. In addition, serotonin and dopamine signalling pathways were found to be significantly altered in TB mice. Serotonin levels in brain showed to be lower in TB mice compared to control mice, while dopamine levels did not change. Moreover, serotonin levels inversely correlated with food intake. Transcriptomic analysis of the hypothalamus of cachectic TB mice with an increased food intake showed changes in NPY, AgRP and serotonin signalling. Serotonin levels in the brain showed to correlate with changes in food intake. Targeting these systems seems a promising strategy to avoid the development of cancer-induced eating disorders.
Hypothalamic food intake regulation in a cancer-cachectic mouse model.
Sex, Specimen part, Treatment
View SamplesInfection with acute and chronic strains of LCMV (Armstrong (ARM) and Clone 13 (C13), respectively) leads to massive proliferation of monocytic cells contemporaneously with peak of the anti-viral CD8+ T cell response. These cells return to nave levels following ARM infection. However, during C13 infection these cells are sustained at high levels and gain a T cell suppressive function at day 14 post infection. The mechanisms by which these cells are induced to proliferate and impair T cell function during chronic LCMV infection are largely unknown. To address this, we analyzed gene expression profiles using microarray analysis of purified splenic monocytic cells (CD11b+ Ly6Chi Gr-1low) from nave mice, or day 14 LCMV ARM or LCMV C13 infected mice.
Chronic but not acute virus infection induces sustained expansion of myeloid suppressor cell numbers that inhibit viral-specific T cell immunity.
Specimen part
View SamplesBackground. Differential gene expression in adipose tissue during diet-induced weight loss followed by a weight stability period is not well characterized. Markers of these processes may provide a deeper understanding of the underlying mechanisms. Objective. To identify differentially expressed genes in human adipose tissue during weight loss and weight maintenance after weight loss. Design. RNA from subcutaneous abdominal adipose tissue from nine obese subjects was obtained and analyzed at baseline, after weight reduction on a low calorie diet (LCD), and after a period of group therapy in order to maintain weight stability. Results. Subjects lost 18.8 + 5.4% of their body weight during the LCD and maintained this weight during group therapy. Insulin sensitivity (HOMA) improved after weight loss with no further improvement during weight maintenance. Cyclin-dependent kinase inhibitor 2B (CDKN2B) and JAZF zinc finger 1 (JAZF1), associated with type 2 diabetes, were downregulated. We could also confirm the downregulation of candidates for obesity and related traits, such as tenomodulin (TNMD) and matrix metallopeptidase 9 (MMP9), with weight loss. The expression of other candidates, such as cell death-inducing DFFA-like effector A (CIDEA) and stearoyl-CoA desaturase (SCD) were upregulated during weight loss but returned to baseline levels during weight maintenance. Conclusion. Genes in the adipose tissue are differentially expressed during weight loss and weight maintenance after weight loss. Genes that show sustained regulation may be of potential interest as markers of the beneficial effects of weight loss whereas others seem to be primarily involved in the process of weight loss itself.
Differential gene expression in adipose tissue from obese human subjects during weight loss and weight maintenance.
Sex, Age
View SamplesThe project used next generation sequencing for RNA-seq analysis, to identify transcriptome changes associated with tumorigenesis in two different caspase-2 knockout mice models. We describe key changes in both lymphoma and neuroblastoma associated genes in the two tumor types that may contribute to tumor outcome following loss of Casp2. We identified a panel of genes with altered expression in Th-MYCN/Casp2-/- tumors, that are strongly associated with neuroblastoma outcome, and which have roles in melanogenesis, Wnt and Hippo pathway signaling, that also contribute to neuronal differentiation. In addition, we found that key changes in gene expression in the EµMyc/Casp2-/- tumors, are associated with increased immune signaling and suggest that Casp2 deficiency augments immune signaling pathways that may be in turn, enhance lymphomagenesis. Overall, our study has identified new genes and pathways that contribute to the caspase-2 tumor suppressor function and highlight distinct roles for caspase-2 in different tissues. Overall design: We used tumors from EµMyc/Casp2-/- mice (which are more aggressive compared to their EµMyc counterarts) as well as tumors from Th-MycN/Casp2-/- mice (which show delayed tumour onset compared to Th-MycN mice) and compared the transcriptomes to their Casp2 wild type counterpart tumors. Sequencing was carried out with Illumina HiSeq 2000 and used short, single-end reads (1x 50bp flow cells) with 4 samples per lane. This yielded approximately 20-30 million raw reads per sample.
Transcriptome profiling of caspase-2 deficient EμMyc and Th-MYCN mouse tumors identifies distinct putative roles for caspase-2 in neuronal differentiation and immune signaling.
Specimen part, Subject
View SamplesGoal of this study is differential gene expression between wild type and Toddler mutant during early zebrafish embryogenesis Overall design: Four timepoints - 4 hours post fertilization (hpf), 5 hpf, 6 hpf, and 7 hpf; one replicate of wild type at each time point, one replicate Toddler mutant at each time point
Toddler signaling regulates mesodermal cell migration downstream of Nodal signaling.
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