E-GEOD-21143
Ontology highlight
ABSTRACT:
OTHER RELATED OMICS DATASETS IN: PRJNA126665
PROVIDER: E-GEOD-21143 | ExpressionAtlas | 2014-08-04
REPOSITORIES: ExpressionAtlas
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Project description:Primary glioblastoma, representing over 90% of adult glioblastoma, develop rapidly without preexisting lower-grade glioma. We have generated a mouse model of primary glioblastoma driven by a single p53 mutation. These p53-mutant gliomas lose the syntenic region of human chromosome 10q, which is mapped to mouse chr19 and chr7. Loss of mouse chr19, containing Pten, activates PI3K/Akt signaling. Rictor/mTORC2 deletion inhibits Akt signaling, causing a significant delay in p53-mutant driven glioma formation. Unexpectedly, Rictor/mTORC2 loss promotes p53-mutant driven medulloblastomas with unique features of pediatric SHH medulloblastoma. Mechanistically, Rictor/mTORC2 loss inhibits the generation of glioma precursor cells from neural stem/progenitor cells in the adult brain, while causing a delay in differentiation of granule cell precursors in the developing brain, a cell-of-origin of SHH medulloblastoma.
2018-06-01 | GSE78895 | GEO
Project description:Mouse embryonic fibroblasts deficient for p53 and expressing mutant RasV12 were infected with lentiviral constructs carrying short hairpin RNAs targeting ARF or a scrambled control. Four days post infection, cells were harvested for microarray analysis.
2013-06-27 | GSE48315 | GEO
Project description:To identify mutant p53 gain-of-function, primary murine osteosarcomas expressing p53 heterozygous mutants were compared to p53 heterozygous tumors. Transcriptomes regulated by different p53 hotspots were used to identify their mechanisms of action. Validation was done in cell line expressing mutant p53, to confirm its binding to transcription factors Stat3 and Egr1.
2022-03-23 | GSE198802 | GEO
Project description:To identify mutant p53 GOF, murine primary osteosarcomas expressing p53R172H or p53R245W over null and p53-null osteosarcomas were processed for bulk sequencing; DEGs were identified in p53R172H and p53R245W expressing tumors by comparing to p53-null tumors; DEGs were used to identify dysregulated pathways and mutant p53 GOF
2023-05-12 | GSE231849 | GEO
Project description:To investigate the mechanisms by which p53 activation triggers developmental defects, we generated a mouse model in which p53 is activated in neural crest cells due to the expression of a mutant p53 protein (p53-25,26) that can bind to and stabilize wild-type p53. Here, we performed gene expression profiling on neural crest cells isolated from these embryos, to identify the transcriptional response to p53 activation during embryogenesis.
2019-07-04 | GSE111753 | GEO
Project description:Our compound (PRIMA) selectively kills tumor cells expressing mutant p53. Here in our study we decided to investigate the impact of our compound on the transcriptome of p53 mutant-expressing cells, Saos2-His273. We plated Saos-2-His273 cells and treated them with our compound for 6h or 12h. We then harvested the cells, extracted the RNA, and followed the protocol to run affymetrix array to analyse the impact of our drug on the whole transcriptome of cells expressing mutant p53.
2009-04-15 | E-GEOD-15368 | biostudies-arrayexpress
Project description:The specific roles of mutant p53’s dominant-negative (DN) or gain-of-function (GOF) properties in regulating acute response and long-term tumorigenesis is unclear. Using “knock-in” mouse strains expressing varying R246S mutant levels, we show that DN effect on transactivation is universally observed after acute p53 activation whereas the effect on cellular outcome is cell-type specific. Reducing mutant p53 levels abrogated the DN effect. Mutant p53’s DN effect protected against radiation-induced death, but did not accentuate tumorigenesis. Furthermore, the R246S mutant did not promote tumorigenesis compared to p53-/- mice in various models, even in the absence of MDM2, unlike the R172H mutant. Together, these data demonstrate that mutant p53’s DN property only affects acute responses, whereas GOF is not universal, being mutation-type specific. Transcriptomes of mouse embryonic fibroblasts harvested from embyros of different p53 genotypes were profiled. A total of 6 primary clones of MEFs were used and these cells were transformed with E1A/Ras. Data was analysed by mixed model ANOVA using Partek.
2012-12-31 | E-GEOD-40416 | biostudies-arrayexpress
Project description:Methylation profiling was performed to assess methylation alterations by the addition of serial oncogenic hits (mutant-IDH1, P53 knockdown and ATRX knockdown) in human neural stem cells.
2017-11-09 | GSE94956 | GEO
Project description:Glioblastoma (GBM) is a highly lethal brain tumor presenting as one of two subtypes with distinct clinical histories and molecular profiles. The primary GBM subtype presents acutely as high-grade disease that typically harbors EGFR, PTEN and Ink4a/Arf mutations, and the secondary GBM subtype evolves from the slow progression of low-grade disease that classically possesses PDGF and p53 events1. Here, we show that concomitant CNS-specific deletion of p53 and Pten in the mouse CNS generates a penetrant acute-onset high-grade malignant glioma phenotype with striking clinical, pathological and molecular resemblance to primary GBM in humans. This genetic observation prompted p53 and PTEN mutational analysis in human primary GBM, demonstrating unexpectedly frequent inactivating mutations of p53 as well the expected PTEN mutations. Integrated transcriptomic profling, in silico promoter analysis and functional studies of murine neural stem cells (NSCs) established that dual, but not singular, inactivation of p53 and Pten promotes an undifferentiated state with high renewal potential and drives elevated c-Myc levels and its associated signature. Functional studies validated increased c-Myc activity as a potent contributor to the impaired differentiation and enhanced renewal of p53-Pten null NSCs as well as tumor neurospheres (TNSs) derived from this model. c-Myc also serves to maintain robust tumorigenic potential of p53-Pten null TNSs. These murine modeling studies, together with confirmatory transcriptomic/promoter studies in human primary GBM, validate a pathogenetic role of a common tumor suppressor mutation profile in human primary GBM and establish c-Myc as a key target for cooperative actions of p53 and Pten in the regulation of normal and malignant stem/progenitor cell differentiation, self-renewal and tumorigenic potential. We used microarrays to detail the gene expression difference of the p53-null and p53/Pten-doubly null neural stem cell after differentiation . Experiment Overall Design: transcriptome comparisons of 2 independent p53-null with 3 p53/Pten double-null murine NSCs at 1 day post exposure to the differentiation inducer.
2008-10-26 | E-GEOD-12694 | biostudies-arrayexpress
Project description:We describe a so far uncharacterized, embryonic and self-renewing Neural Plate Border Stem Cell (NBSC) population with the capacity to differentiate into central nervous and neural crest lineages. NBSCs can be obtained by neural transcription factor-mediated reprogramming (BRN2, SOX2, KLF4, and ZIC3) of human adult dermal fibroblasts and peripheral blood cells (induced Neural Plate Border Stem Cells, iNBSCs) or by directed differentiation from human induced pluripotent stem cells. Moreover, human (i)NBSCs share molecular and functional features with an endogenous NBSC population isolated from neural folds of E8.5 mouse embryos. Upon differentiation, iNBSCs give rise to either (1) radial glia-type stem cells, dopaminergic and serotonergic neurons, motoneurons, astrocytes, and oligodendrocytes or (2) cells from the neural crest lineage. Here we provide array-based expression data of primary mouse Neural Plate Border Stem Cells (pNBSCs) derived from E8.5 mouse embryos and radial glia-type stem cells and neural crest progenitors derived thereof. The data provided reveal that pNBSCs can be directed into defined neural cell types of the CNS- and neural crest lineage.
2018-12-20 | E-MTAB-5805 | biostudies-arrayexpress