Similar Datasets
Project description:RNA sequencing on primary murine chondrocytes expressing mutant Idh1
| PRJNA507610 | ENA
Project description:The aim of ths study is to compare global methylation status between 1) IDH1 mutant and IDH1/2 wild-type glioblastoma tumorsphere cells and 2) MGG152 (IDH1 mutant) with DMSO and IDH1 inhibitor treatment. Genome wide DNA methylation profiling of patient derived glioblastoma tumorsphere and HT1080 cells. The Illumina Infinium Human DNA methylation Beadchip450 was used to obtain DNA methylation profiles. Bisulphite converted DNA from the 10 samples and one control were hybridised to the Illumina Infinium Human Methylation Beadchip450. Please note that the MGG (in the sample title) represents patient-derived MGH glioblastoma cell lines. Regarding MGG152 samples, sample no.1 is low passage number and used for comparison between IDH1 mt and wild-type. Sample no. 2-4 were used for assessing DNA methylation change after short term or long term IDH1 inhibiting treatment.
2015-09-22 | E-GEOD-73270 | biostudies-arrayexpress
Project description:Mutations in the IDH1 and IDH2 genes encoding isocitrate dehydrogenases are frequent in human glioblastomas1 and cytogenetically normal acute myeloid leukemias (AML)2. These alterations are gain-of-function mutations in that they drive the synthesis of the M-bM-^@M-^\oncometaboliteM-bM-^@M-^] R-2-hydroxyglutarate (2HG)3. It remains unclear how IDH1 and IDH2 mutations modify myeloid cell development and promote leukemogenesis. Here we report the characterization of conditional knock-in mice in which the most common IDH1 mutation, Idh1-R132H, is inserted into the endogenous murine Idh1 locus and is expressed in cells of the hematopoietic (Vav-KI) or more specifically in cells of the myeloid (LysM-KI) lineage. These mutants show increased numbers of early hematopoietic progenitors and develop splenomegaly and anemia with extramedullary hematopoiesis, suggesting a dysfunctional bone marrow niche. Furthermore, LysM-KI cells exhibit both hypermethylated histones and changes to DNA methylation similar to those observed in human IDH1/2-mutant AML. Thus, our study is the first to describe the generation of conditional Idh1-R132H-KI mice. Furthermore, our study is also the first report showing the induction of a leukemic DNA methylation signature in a modeled system and sheds light on the mechanistic links between IDH1 mutation and human AML. DNA methylation profiling in LSK cells from IDH1-R132H knock-in mice vs. control mice
2012-07-22 | E-GEOD-38687 | biostudies-arrayexpress
Project description:Mutations in the IDH1 and IDH2 genes encoding isocitrate dehydrogenases are frequent in human glioblastomas1 and cytogenetically normal acute myeloid leukemias (AML)2. These alterations are gain-of-function mutations in that they drive the synthesis of the “oncometabolite” R-2-hydroxyglutarate (2HG)3. It remains unclear how IDH1 and IDH2 mutations modify myeloid cell development and promote leukemogenesis. Here we report the characterization of conditional knock-in mice in which the most common IDH1 mutation, Idh1-R132H, is inserted into the endogenous murine Idh1 locus and is expressed in cells of the hematopoietic (Vav-KI) or more specifically in cells of the myeloid (LysM-KI) lineage. These mutants show increased numbers of early hematopoietic progenitors and develop splenomegaly and anemia with extramedullary hematopoiesis, suggesting a dysfunctional bone marrow niche. Furthermore, LysM-KI cells exhibit both hypermethylated histones and changes to DNA methylation similar to those observed in human IDH1/2-mutant AML. Thus, our study is the first to describe the generation of conditional Idh1-R132H-KI mice. Furthermore, our study is also the first report showing the induction of a leukemic DNA methylation signature in a modeled system and sheds light on the mechanistic links between IDH1 mutation and human AML.
2012-07-22 | GSE38687 | GEO
Project description:Sorted tumor RNA-seq of syngeneic murine mutant IDH1 ICC tumor model treated with IDH1 inhibitor against vehicle
| PRJEB48486 | ENA
Project description:IDH1 is the most commonly mutated metabolic gene across human cancers, with the highest mutational frequency observed in AML, glioma, chondrosarcoma, and intrahepatic cholangiocarcinoma. Mutations of the hot spot R132 codon alter the activity of the IDH1 enzyme, resulting in the NADPH-dependent conversion of alpha-ketoglutarate to (R)-2-hydroxyglutarate [(R)-2HG], which accumulates to mM levels within tumors. (R)-2HG competitively inhibits a range of enzymes that utilize alpha-ketoglutarate. Targets include the JmjC family histone demethylases and TET family DNA demethylases whose inhibition is linked to the altered epigenetic state characteristic of many mIDH tumors. To gain insight into the mechanisms underlying the anti-tumor efficacy of inhibition of mutant IDH1 we conducted RNA-sequencing (RNA-seq) analysis of purified tumor cells. For these studies, the immune-competent 2205 subcutaneous allograft model was treated with AG120 or vehicle for 6 days and non-tumor cells were removed by magnetic bead sorting (negative selection for CD45+ immune cells, CD31+ endothelial cells, TER119+ erythrocytes, and CD90.2+ fibroblasts).
2021-11-23 | E-MTAB-11112 | biostudies-arrayexpress
Project description:MeRIP-Seq data aligned to the genome (GRCh38) for cells with IDH1-Mut or IDH1-WT genotypes. Aligned data (BAM) are separated into input RNA and m6A immunoprecipitated RNA for each cell sample.
2024-02-19 | E-MTAB-13765 | biostudies-arrayexpress
Project description:The aim of ths study is to compare global methylation status between 1) IDH1 mutant and IDH1/2 wild-type glioblastoma tumorsphere cells and 2) MGG152 (IDH1 mutant) with DMSO and IDH1 inhibitor treatment. Genome wide DNA methylation profiling of patient derived glioblastoma tumorsphere and HT1080 cells. The Illumina Infinium Human DNA methylation Beadchip450 was used to obtain DNA methylation profiles.
2015-09-22 | GSE73270 | GEO
Project description:Transcriptional profiling of mouse chondrocytes comparing chondrocytes infected with empty adenovirus and Epas1 adenovirus. RNA was extracted from each chondrocytes. We used microarrays to determine the effect of Epas1 overexpression on chondrocytes and identify the noble regulatory molecules during osteoarthritic pathogenesis.
2015-10-02 | GSE73659 | GEO
Project description:The R132H mutation in the metabolic enzyme isocitrate dehydrogenase 1 (IDH1) is the most important prognostic factor for survival of glioma patients. This resulted in many studies investigating the effects of this mutation, including those on energy metabolism. This led to the discovery of a panel of enzymes mainly involved in glutamate anaplerosis and aerobic glycolysis that change in abundance as a result of the IDH1 mutation. To further study these changes and investigate the therapeutic value of inhibitors of IDH1 R132H-associated metabolic pathways, appropriate glioma models are required that mimic in vivo metabolism as good as possible. To investigate how metabolism is affected by in vitro cell culture, we here compared surgically obtained snap frozen glioma tissues with their corresponding primary glioma cell culture models with a previously developed targeted mass spectrometry proteomic assay. We determined the relative abundance of a panel of metabolic enzymes. Results confirmed increased glutamate use and decreased aerobic glycolysis in resected IDH1 R132H glioma tissue samples. However, these metabolic profiles were not reflected in the paired glioma culture samples. Analysis of orthotopic glioma xenograft samples with and without the IDH1 mutation revealed metabolic profiles that more closely resembled clinical counterparts. We suggest that culture conditions and tumor microenvironment play a crucial role in maintaining the in vivo metabolic situation in cell culture models. For this reason, new models that more closely resemble the in vivo microenvironment, such as 3-dimensional cell co-cultures or organotypic multicellular spheroid models, need to be developed and investigated.
2022-02-14 | PXD024009 | Pride