Glioblastomas (GBM) are brain tumors which display a bad prognosis despite conventional treatment associating surgical resection and subsequent radio-chemotherapy. These tumors are defined by an abundant and abnormal vascularization as well as by an important cellular heterogeneity. GBM notably contain a subpopulation of GBM stem-like cells (GSC) which contribute to tumor aggressiveness, resistance, and recurrence. Moreover, GSC directly take part in the formation of new vessels via their transdifferentiation into tumor derived endothelial cells (TDEC). Considering the importance of the vascularization in the GBM, we postulate that radiation could enhance the transdifferentiation of GSC into TDEC. Here, we show that ionizing radiation potentiates endothelial features of TDEC obtained from 3 patient-derived primocultures of GSC. Indeed, TDEC obtained from irradiated GSC (TDEC IR+) migrate more towards VEGF, form more pseudotubes in Matrigel in vitro and develop more functional blood vessel in Matrigel plugs implanted in Nude mice than TDEC obtained from non-irradiated GSC. Transcriptomic analysis allows us to highlight an overexpression of Tie2 in TDEC IR+ which is associated with the activation of AKT signaling pathway. All radiation-induced effects on TDEC IR+ were abolished by using a Tie2 kinase inhibitor, confirming the role of Tie2 signaling pathway in this process. Finally, the number of Tie2+ vessels is increased in recurrent GBM compared with matched untreated tumors. In conclusion, we show that irradiation potentiates proangiogenic features of TDEC throught Tie2/AKT signaling pathway. New therapeutic stategies associating standard teatment and an inhibitor of Tie2 signaling pathway should be considered for forthcoming trials.
Ionizing radiation induces endothelial transdifferentiation of glioblastoma stem-like cells through the Tie2 signaling pathway.
Specimen part
View SamplesClinical symptoms of dengue virus (DENV) infection, the most prevalent arthropod-borne viral disease, range from classical mild dengue fever to severe, life-threatening dengue shock syndrome. However, most DENV infections cause few or no symptoms. Asymptomatic DENV-infected patients provide a unique opportunity to decipher the host immune responses leading to virus elimination without negative impact on an individuals health. We used an integrated approach of transcriptional profiling and immunological analysis to compare a Cambodian population of strictly asymptomatic viremic individuals with clinical dengue patients. Whereas inflammatory pathways and innate immune response pathways were similar between asymptomatic individuals and clinical dengue patients, expression of proteins related to antigen presentation and subsequent T and B cell activation pathways were differentially regulated, independent of viral load and previous DENV infection history. Feedback mechanisms controlled the immune response in asymptomatic viremic individuals, as demonstrated by increased activation of T cell apoptosis-related pathways and FcRIIB signaling associated with decreased anti-DENV specific antibody concentrations. Taken together, our data illustrate that symptom-free DENV infection in children is associated with determined by increased activation of the adaptive immune compartment and proper control mechanisms, leading to elimination of viral infection without excessive immune activation, with implications for novel vaccine development strategies
Increased adaptive immune responses and proper feedback regulation protect against clinical dengue.
Sex, Age, Specimen part, Disease, Disease stage
View SamplesThis experiment was performed to identify immediate early genes that were induced by PDGF specifically through Src family kinases (SFKs), MEK1/2, or PI 3-K.
Platelet-derived growth factor stimulates Src-dependent mRNA stabilization of specific early genes in fibroblasts.
No sample metadata fields
View SamplesCellular and tissue defects associated with insulin resistance are coincident with transcriptional abnormalities and are improved after insulin sensitization with thiazolidinedione (TZD) PPAR ligands.
Mechanisms of human insulin resistance and thiazolidinedione-mediated insulin sensitization.
Specimen part, Subject
View SamplesSystemic arterial smooth muscle cells are exposed to a broad range of oxygen concentrations under physiological conditions. Hypoxia can modulate the proliferative response of smooth muscle cells leading to speculation about its role in vasculogenesis, vascular remodelling and the pathogenesis of arterial disease. The effect of hypoxia has been inconsistent, however, with both enhanced proliferation and growth arrest reported. Nevertheless, these reports support an important effect of hypoxia on smooth muscle cell proliferation and, given its physiological and clinical relevance, this requires clarification. We posited that variation in O2 concentration, within the range that exists in vivo, may have different effects on the proliferation and survival of vascular smooth muscle cells.
Oxygen regulation of arterial smooth muscle cell proliferation and survival.
No sample metadata fields
View SamplesThe behavior of yeast cells during industrial processes such as the production of beer, wine and bioethanol has been extensively studied. By contrast, our knowledge about yeast physiology during solid state processes, such as bread dough, cheese or cocoa fermentation remains limited. We investigated changes in the transcriptome of three genetically distinct Saccharomyces cerevisiae strains during bread dough fermentation. Our results show that regardless of the genetic background, all three strains exhibit similar changes in expression patterns. At the onset of fermentation, expression of glucose-regulated genes changes dramatically, and the osmotic stress response is activated. The middle fermentation phase is characterized by the induction of genes involved in amino acid metabolism. Finally, at the latest time point, cells suffer from nutrient depletion and activate pathways associated with starvation and stress response. Further analysis shows that genes regulated by the High Osmolarity Glycerol (HOG) pathway, the major pathway involved in the response to osmotic stress and glycerol homeostasis, are among the most differentially expressed genes at the onset of fermentation. More importantly, deletion of HOG1 and other genes of this pathway significantly reduces fermentation capacity. Together, our results demonstrate that cells embedded in a solid matrix such as bread dough suffer severe osmotic stress, and that a proper induction of the HOG pathway is critical for an optimal fermentation.
Dynamics of the Saccharomyces cerevisiae transcriptome during bread dough fermentation.
No sample metadata fields
View SamplesInterferon (IFN) is a unique type I IFN that is not induced by pattern-recognition response elements. IFN is constitutively expressed in mucosal tissues including the female genital mucosa. We show here that IFN induces an antiviral state in human macrophages that blocks HIV-1 replication.
IFN-<b>ε</b> protects primary macrophages against HIV infection.
Specimen part, Treatment, Time
View SamplesB-methylthiolation of the Escherichia coli Ribosomal Protein S12 Regulates Anaerobic Gene Expression.
A proteomic and transcriptomic approach reveals new insight into beta-methylthiolation of Escherichia coli ribosomal protein S12.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Multi-level omics analysis in a murine model of dystrophin loss and therapeutic restoration.
Specimen part, Treatment
View SamplesDuchenne muscular dystrophy (DMD) is a classical monogenic disorder, a model disease for genomic studies and a priority candidate for regenerative medicine and gene therapy. Although the genetic cause of DMD is well known, the molecular pathogenesis of disease and the response to therapy are incompletely understood. Here,we describe analyses of protein, mRNA and microRNA expression in the tibialis anterior of the mdx mouse model of DMD. Notably, 3272 proteins were quantifiable and 525 identified as differentially expressed in mdx muscle (P < 0.01). Therapeutic restoration of dystrophin by exon skipping induced widespread shifts in protein and mRNA expression towards wild-type expression levels, whereas the miRNome was largely unaffected. Comparison analyses between datasets showed that protein and mRNA ratios were only weakly correlated (r = 0.405), and identified a multitude of differentially affected cellular pathways, upstream regulators and predicted miRNAtarget interactions. This study provides fundamental new insights into gene expression and regulation in dystrophic muscle.
Multi-level omics analysis in a murine model of dystrophin loss and therapeutic restoration.
Specimen part, Treatment
View Samples