This SuperSeries is composed of the SubSeries listed below.
Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin.
Specimen part
View SamplesThe cell of origin in glioblastoma is not formally proven but generally accepted to be a neural stem cell or glial precursor cell. In addition, there is also limited knowledge about the functional consequences of the cell of origin for glioblastoma development and response to therapy.
Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin.
Specimen part
View SamplesThe cell of origin in glioblastoma is not formally proven but generally accepted to be a neural stem cell or glial precursor cell. In addition, there is also limited knowledge about the functional consequences of the cell of origin for glioblastoma development and response to therapy.
Glioblastoma Cell Malignancy and Drug Sensitivity Are Affected by the Cell of Origin.
Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition.
Specimen part, Cell line
View SamplesIntra-tumor heterogeneity is a hallmark of glioblastoma multiforme, and thought to negatively affect treatment efficacy. Here we establish libraries of glioma-initiating cell (GIC) clones from patient samples and find extensive molecular and phenotypic variability between clones, including a wide range of responses to radiation and drugs. This widespread variability was observed as a continuum of multitherapy resistance phenotypes linked to a proneural-to-mesenchymal shift in the transcriptome.
Clonal Variation in Drug and Radiation Response among Glioma-Initiating Cells Is Linked to Proneural-Mesenchymal Transition.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes.
Disease, Cell line
View SamplesTo explore the degree to which the glioma cell lines remained transcriptionally stable under diverse experimental conditions, we transplanted three different lines (U3020MG, U3047MG and U3065MG) intracranially to NOD-SCID mice; explanted the resulting tumors and cultured the cells for two passages, and then isolated RNA from the cell line prior to transplantation (U3020MG-p10, U3047MG-p7, U3065MG-p10), from the xenograft tumor and from the explanted cells.
The Human Glioblastoma Cell Culture Resource: Validated Cell Models Representing All Molecular Subtypes.
Disease
View SamplesAims/hypothesis: While lipid deposition in skeletal muscle is considered to be involved in obesity-associated insulin resistance, neutral intramyocellular lipid (IMCL) accumulation per se does not necessarily induce insulin resistance. We previously demonstrated that overexpression of the lipid droplet coat protein perilipin 2 augments intramyocellular lipid content while improving insulin sensitivity. Another member of the perilipin family, perilipin 5 (PLIN5), is predominantly expressed in oxidative tissues like skeletal muscle. Here we investigated the effects of PLIN5 overexpression in comparison with effects of PLIN2 on skeletal muscle lipid levels, gene expression profiles and insulin sensitivity. Methods: Gene electroporation was used to overexpress PLIN5 in tibialis anterior muscle of rats fed a high fat diet. Eight days after electroporation, insulin-mediated glucose uptake in skeletal muscle was measured by means of a hyperinsulinemic euglycemic clamp. Electron microscopy, fluorescence microscopy and lipid extractions were performed to investigate IMCL accumulation. Gene expression profiles were obtained using microarrays. Results: TAG storage and lipid droplet size increased upon PLIN5 overexpression. Despite the higher IMCL content, insulin sensitivity was not impaired and DAG and acylcarnitine levels were unaffected. In contrast to the effects of PLIN2 overexpression, microarray data analysis revealed a gene expression profile favoring FA oxidation and improved mitochondrial function. Conclusions/interpretation: Both PLIN2 and PLIN5 increase neutral IMCL content without impeding insulin-mediated glucose uptake. As opposed to the effects of PLIN2 overexpression, overexpression of PLIN5 in skeletal muscle promoted expression of a cluster of genes under control of PPAR and PGC1 involved in FA catabolism and mitochondrial oxidation.
Overexpression of PLIN5 in skeletal muscle promotes oxidative gene expression and intramyocellular lipid content without compromising insulin sensitivity.
Sex, Age, Specimen part, Treatment
View Samples1,2-unsaturated pyrrolizidine alkaloids (PA) are plant metabolites predominantly occurring in the plant families Asteraceae and Boraginaceae. Acute and chronic PA poisoning causes severe hepatotoxicity. So far, the molecular mechanisms of PA toxicity are not well understood. To analyze its mode of action, primary human hepatocytes were exposed to a non-cytotoxic dose of 100 M of four structurally different PA: echimidine, heliotrine, senecionine, senkirkine. Changes in mRNA expression were analyzed by a whole genome microarray. Employing cut-off values with a |fold change| of 2 and a q-value of 0.01, data analysis revealed numerous changes in gene expression. In total, 4556, 1806, 3406 and 8623 genes were regulated by echimidine, heliotrine, senecione and senkirkine, respectively. 1304 genes were identified as commonly regulated. PA affected pathways related to cell cycle regulation, cell death and cancer development. The transcription factors TP53, MYC, NFB and NUPR1 were predicted to be activated upon PA treatment. Furthermore, gene expression data showed a considerable interference with lipid metabolism and bile acid flow. The associated transcription factors FXR, LXR, SREBF1/2, and PPAR// were predicted to be inhibited. In conclusion, though structurally different, all four PA significantly regulated a great number of genes in common. This proposes similar molecular mechanisms, although the extent seems to differ between the analyzed PA as reflected by the potential hepatotoxicity and individual PA structure.
Disturbance of gene expression in primary human hepatocytes by hepatotoxic pyrrolizidine alkaloids: A whole genome transcriptome analysis.
No sample metadata fields
View SamplesType 2 diabetes is characterized by excessive lipid storage in skeletal muscle. Excessive intramyocellular lipid storage exceeds intracellular needs and induces lipotoxic events ultimately contributing to the development of insulin resistance. Lipid droplet (LD)-coating proteins may control proper lipid storage in skeletal muscle. Perilipin 2 (PLIN2/ADRP) is one of the most abundantly expressed LD-coating proteins in skeletal muscle. Here we examined the role of PLIN2 in myocellular lipid handling and insulin sensitivity by investigating the effects of in vitro PLIN2 knockdown and in vitro and in vivo overexpression. PLIN2 knockdown decreased LD formation and triacylglycerol storage, marginally increased FA oxidation, and increased incorporation of palmitate into diacylglycerols and phospholipids. PLIN2 overexpression in vitro increased intramyocellular TAG storage paralleled with improved insulin sensitivity. In vivo muscle-specific PLIN2 overexpression resulted in increased LD accumulation and blunted the high-fat diet-induced increase of OXPHOS protein content. Diacylglycerol levels were unchanged, while ceramide levels were increased. Despite the increased intramyocellular lipid accumulation, PLIN2 overexpression improved skeletal muscle insulin sensitivity. We conclude that PLIN2 is essential for lipid storage in skeletal muscle by enhancing the partitioning of excess FAs towards triacylglycerol storage in LDs thereby blunting lipotoxicity-associated insulin resistance.
Perilipin 2 improves insulin sensitivity in skeletal muscle despite elevated intramuscular lipid levels.
Cell line
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