Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA348745 | ENA |
REPOSITORIES: ENA
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Project description:Mouse neural stem cells were generated from conditional knock-in mice. Mutant IDH1 is conditionally expressed following expression of Cre-recombinase. Cre-recombinase was incorporated in vitro via adenoviral-Cre recombinase. Addtionally, adenoviral-GFP was also used to control for effects of adenoviral infection. D-2HG, the metabolic product of IDH1-R132H, was detected in cell lines post-cre transduction
2017-08-22 | GSE88828 | GEO
Project description:4C-seq was performed to assess genomic contacts with the SOX2 protmoter, human neural stem cells with no oncogenic alterations were compared to those with concurrent IDH1-R132H overexpression, P53 shRNA knockdown and ATRX shRNA knockdown.
2017-11-09 | GSE94961 | GEO
Project description:Human astrocytomas and oligodendrogliomas are defined by mutations in the metabolic enzyme isocitrate dehydrogenase (IDH) 1 or 2. Mutant IDH1 causes the production and accumulation of the metabolite 2 hydroxyglutarate, which induces genome-wide hypermethylation, and is thought to be a driver mutation of these tumours. However, there are multiple contradictory effects of mutant IDH1 in cell lines and in vivo models, prompting us to study the effect of mutant IDH1 on cell differentiation, proliferation, and apoptosis. Here we established mouse glioma initiating cells (GIC) by inactivating the tumour suppressor genes Pten and p53 in the neural stem/progenitor cell population of the forebrain, and compared these GIC with triple mutant tumours expressing in addition the Idh1 R132H mutation. We found that Idh1 mutant cells proliferate less in vitro and mice with Idh1 mutant tumour survived significantly longer than their Idh1 wild type counterparts. By comparing the miRNA expression profiles of Idh wild-type and Idh mutant cells and tumours we identified miR-183-5p as a differentially expressed miRNA.
2019-08-22 | GSE119740 | GEO
Project description:To investigate whether IDH1 mutation influence the effects of oncolytic virus VSVΔ51, we transduced doxycycline-inducible IDH1-R132H lentiviruses into LN-229 to establish the LN-229-TRE-R132H cell line. We then performed gene expression profiling analysis using data obtained from RNA-seq of LN-229-TRE-R132H cells infected with or without VSVΔ51 in the presence or absence of IDH1 mutation induced by doxycycline.
2023-09-19 | GSE208634 | GEO
Project description:Human astrocytomas and oligodendrogliomas are defined by mutations in the metabolic enzyme isocitrate dehydrogenase (IDH) 1 or 2. Mutant IDH1 causes the production and accumulation of the metabolite 2 hydroxyglutarate, which induces genome-wide hypermethylation, and is thought to be a driver mutation of these tumours. However, there are multiple contradictory effects of mutant IDH1 in cell lines and in vivo models, prompting us to study the effect of mutant IDH1 on cell differentiation, proliferation, and apoptosis. Here we established mouse glioma initiating cells (GIC) by inactivating the tumour suppressor genes Pten and p53 in the neural stem/progenitor cell population of the forebrain, and compared these GIC with triple mutant tumours expressing in addition the Idh1 R132H mutation. We found that Idh1 mutant cells proliferate less in vitro and mice with Idh1 mutant tumour survived significantly longer than their Idh1 wild type counterparts. By comparing the RNA expression profiles of Idh wild-type and Idh mutant cells and tumours we identified endoplasmic reticulum stress pathways were significantly associated with Idh1 mutation.
2019-08-22 | GSE119741 | GEO
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:The cytosolic NADP+-dependent isocitrate dehydrogenase IDH1 is frequently mutated in human cancers. Recent studies have shown that IDH1 mutant primary glioblastomas (GBM) and acute myeloid leukemias (AML) display robust association with CpG island methylator phenotype (CIMP). Such observations bring into question whether IDH1 mutations directly contribute to the development of CIMP or if the hypermethylation phenotype precedes acquisition of IDH1 mutations. To reveal the effects of IDH1 mutations on DNA methylation and gene expression, we introduced the most frequently observed IDH1 mutation, R132H, into a human cancer cell line through gene targeting. We profiled changes in methylation at over 27,000 CpG dinucleotides spanning 14,475 unique gene regions and characterized genome-wide gene expression alterations resulting from IDH1R132H knockin. We observed consistent changes in both DNA methylation and gene expression when comparing two independent IDH1R132H knockin clones to their wild-type parent, and report hypermethylation of over 2,000 loci, the majority of which contained preexisting methylation in IDH1WT parental cells. These loci exhibit the same trend in primary TCGA glioblastoma tumors with mutant IDH1 as compared to those with wild-type IDH1 and have significant overlap with genes hypermethylated in glioma-CIMP+ tumors. Furthermore, we identify specific DNA methylation and gene expression alterations which correlate with IDH1 mutations in our cell-line model as well as primary glioblastomas, including hypermethylation and transcriptional silencing of RBP1. The presented data provide insight on epigenetic alterations induced by IDH1 mutations and support a contributory role for IDH1 mutants in regulation of DNA methylation and gene expression in human cancer cells. Comparison of IDH1 R132H and wild-type HCT116 cells as well as HOG cells overexpressing either wild-type IDH1 or IDH1 R132H
2012-08-13 | E-GEOD-31133 | biostudies-arrayexpress
Project description:IDH1-R132H is expressed in Low Grade Glioma (LGG) in combination with mutation in ATRX and TP53 genes. IDH1-R132H results in gain of function with production of 2-hydroxygluatrate, that in turn generates a hypermethylatyed phenotype in DNA and histone with consequences in epigenetic regulation of gene expression. Here we will compare the gene expression profile between IDH1-R132H and IDH1 Wt tumor neurospheres.
2019-03-18 | GSE94974 | GEO
Project description:U87 cells were transduced with IDH1 WT or IDH1 R132H and stable clones were selected.
2018-07-12 | GSE101291 | GEO
Project description:DNA methylation in Vav-IDH1-KI mouse haematopoietic stem cells
| PRJNA277224 | ENA