Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA753972 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR15458541_1.fastq.gz | Fastqsanger.gz | |||
| SRR15458541_2.fastq.gz | Fastqsanger.gz | |||
| SRR15458542_1.fastq.gz | Fastqsanger.gz | |||
| SRR15458542_2.fastq.gz | Fastqsanger.gz | |||
| SRR15458543_1.fastq.gz | Fastqsanger.gz |
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Project description:Mosaic Analysis with Double Markers (MADM) based glioma mouse model, which homozygously lacks Tp53 and Nf1, spontaneously developed gliomas at the post-natal 90-120 days. Tp53 and Nf1 are among the most frequently mutated genes in human glioma patients. Investigating the expression changes of genes induced by inactivation of Tp53 and Nf1 can be a clue to clarify the mechanism of gliomagenesis. We examined the expressions of glioma in MADM mouse at post-natal 150 days (n=3) and of normal brain in Tp53 and Nf1 wild type mouse at post-natal 150 days (n=2). We used SurePrint G3 Mouse GE 8×60K array slides (G4858A, Agilent Technologies).
2017-06-30 | GSE91050 | GEO
Project description:Mosaic Analysis with Double Markers (MADM) based glioma mouse model, which homozygously lacks Tp53 and Nf1, spontaneously developed gliomas at the post-natal 90-120 days. Tp53 and Nf1 are among the most frequently mutated genes in human glioma patients. Investigating the changes of histone modifications induced by inactivation of Tp53 and Nf1 can be a clue to clarify the mechanism of gliomagenesis. We examined the histone modifications of glioma in MADM mouse at post-natal 150 days (n=3) and post-natal 8 days (n=1) and NSC, astrocyte derived from normal mice brain (both n=1) ). We used customized SurePrint G3 Mouse GE 2×400K array slides (G4858A, Agilent Technologies).
2020-02-20 | GSE110926 | GEO
Project description:Mosaic Analysis with Double Markers (MADM) based glioma mouse model, which homozygously lacks Tp53 and Nf1, spontaneously developed gliomas at the post-natal 90-120 days. Tp53 and Nf1 are among the most frequently mutated genes in human glioma patients. Investigating the expression changes of genes induced by inactivation of Tp53, Nf1 and EZH2 can be a clue to clarify the mechanism of gliomagenesis. We examined the expressions of glioma cells in MADM mouse (n=2), EZH2 knocked-out MADM glioma tissues (n=3) and neural stem cell (NSC), astrocyte established with normal mice brains (n=2, respectively) and TP53 knocked-out astrocytes, derived from TP53 knocked-out mice (n=2). We used SurePrint G3 Mouse GE 8×60K array slides (G4858A, Agilent Technologies).
2020-02-20 | GSE110927 | GEO
Project description:The paucity of genetically informed, immune-competent tumor models impedes evaluation of conventional, targeted, and immune therapies. By engineering mouse fallopian tube (FT) organoids using lentiviral gene transduction and/or CRISPR/Cas9 mutagenesis, we generated multiple high grade serous ovarian carcinoma (HGSOC) models exhibiting combinations of mutations seen in patients. Detailed analysis of homologous recombination (HR)-proficient (Tp53-/-;Ccne1OE;Akt2OE ;KrasOE), HR-deficient (Tp53-/-;Brca1-/-;MycOE ) and unclassified (Tp53-/-;Pten-/-;Nf1-/-) examples revealed differences in in vitro properties and tumorigenicity/metastasis. Tumorigenic organoids had differential sensitivity to HGSOC chemotherapeutics and evoked distinct immune microenvironments. These findings enabled development of a chemotherapy/immunotherapy regimen that yielded durable, T-cell dependent responses in Tp53-/-;Ccne1OE;Akt2OE;Kras HGSOC; by contrast, Tp53-/-;Pten-/-;Nf1-/- tumors failed to respond. Genotype-informed, syngeneic organoid models could provide an improved platform for rapid evaluation of tumor biology and therapeutics.
2020-11-08 | GSE147276 | GEO
Project description:The deubiquitinating enzyme BAP1 is a tumour suppressor, amongst others involved in cholangiocarcinoma. BAP1 has many proposed molecular targets, while its Drosophila homolog is known to deubiquitinate Histone H2AK119. Here, we mutate BAP1 by CRISPR/Cas9 in normal human liver organoids. We find that BAP1 controls the expression of junctional/cytoskeleton components by regulating chromatin accessibility. Consequently, we observe loss of multiple epithelial characteristics, while motility increases. Importantly, restoring the catalytic activity of BAP1 in the nucleus rescues these cellular and molecular changes. We engineer human liver organoids to combine four common cholangiocarcinoma mutations (TP53, PTEN, SMAD4, NF1). In this genetic background, BAP1 loss results in acquisition of malignant features upon xenotransplantation. Thus, control of epithelial identity through the regulation of chromatin accessibility appears a key aspect of BAP1’s tumour suppressor function. Organoid technology combined with CRISPR/Cas9 provides an experimental platform for mechanistic studies of cancer gene function in a human context.
2019-05-22 | PXD013353 | Pride
Project description:Background: Signaling by receptor tyrosine kinases (RTK) is frequently dysregulated in gliomas. Inter-individual variability in the causes for dysregulated RTK signaling may have hampered the efficacy of targeted therapies. Using gene expression modules around key regulators in the RAS-RAF-MEK-MAPK cascade and in the phosphatidylinositol 3-kinase-AKT pathways, we developed a âRMPAâ clustering scheme to distinguish gliomas with varying extents of RTK signaling. Results: We identified gene modules consistently co-expressed with NF1 (NF1-M), Sprouty (SPRY-M) and PTEN (PTEN-M) in gliomas. Their signatures enabled robust clustering of adult diffuse gliomas of WHO grades II-IV into RMPAhigh and RMPAlow phenotypes in a morphology-independent manner. In five independent data sets from three continents containing more than 1500 adult diffuse gliomas, RMPAhigh gliomas were associated with poor prognosis while RMPAlow gliomas were not. The RMPAhigh and RMPAlow glioma subtypes showed distinct levels of the activities of RAS-RAF-MEK-MAPK cascade and PI3K-AKT pathway and harbored unique sets of genomic alterations in the RTK signaling-related genes. The RMPAhigh gliomas contained large numbers of immature vessel cells and tumor associated macrophages and both cell types expressed high levels of pro-angiogenic RTKs including MET, VEGFR1, KDR, EPHB4 and NRP1. Conclusion: Inter-glioma variability in RTK signaling activities can be defined using the RMPA clustering scheme. The combined signatures of NF1-M, SPRY-M and PTEN-M reflect RTK signaling activity both in the glioma cells and in the glioma microenvironment. Our data show that RTK signaling in the glioma microenvironment may play a pivotal role in glioma progression. Transcriptome data from 22 fresh gliomas (2 astrocytoma II, 1 oligodendrocytoma II, 7 oligoastrocytoma II, 4 anaplastic oligoastrocytoma III and 8 GBM) were obtained using Affymetrix Human Gene 1.0 ST Array. Unsupervised hierarchical clustering of the expression data for the SPRY-M, NF1-M and PTEN-M was performed on these transcriptome data to identify samples with RMPAhigh or RMPAlow signature.
2015-10-30 | E-GEOD-74462 | biostudies-arrayexpress
Project description:In order to understand the relationships between the human non-GCIMP glioblastoma subgroups, we performed computational analysis of human genomic data to predict the temporal sequence in which the driver events arise during tumorigenesis. The order of evolutionary events for non-GCIMP GBM is 1) chr 7 gain and loss of chr 10, followed by 2) CDKN2A loss and/or TP53 mutation, and 3) alterations canonical for specific subtypes such as NF1 loss or focal amplification of PDGFRα or EGFR. We then developed a computational methodology to identify the drivers of broad copy number changes, identifying PDGF-A (chr 7) and PTEN (chr 10) as driving the initial non-disjunction events. These predictions were validated using mouse modeling, showing PDGF-A is sufficient to induce PN-like gliomas that are enhanced by loss of Ink4a-Arf, Tp53 or Pten. Additional Nf1 loss converts PN to the MES subtype. Our findings suggest non-GCIMP GBMs arise as, and evolve from, a common proneural-like precursor. hGBM_sphere: Three different human GBM sphere lines expressing two different NF1-shRNAs or empty shRNA-control were generated by a lentiviral infection with the relevant pLKO.1 vectors. The total RNAs were obtained from the GBM sphere lines and the gene expression profile of the NF1-shRNA cells was then compared to the control cells. hGBM_rapamycin: Two human GBM sphere lines (TS543 and TS667) expressing the NF1-shRNAs were generated by a lentiviral infection with two different pLKO.1-NF1-shRNA vectors (two different target sequence; #2 and #5). The total RNAs were obtained from the NF1-shRNA lines treated with a 1nM rapamycin or 0.1% DMSO control for 5 hours and the gene expression profile was then compared between the both groups. Murine_gliomas: Murine brain tumors were generated by an injection of DF1 cells producing the relevant RCAS virus into newborn pups or adult mice brain. When mice presented any symptoms of disease, the mice were sacrificed and the brain tumor tissues were macroscopically dissected. Then total RNAs were extracted from the murine brain tumors or normal brain tissues and the gene expression profile was compared between various tumor types and/or normal brain tissues. In this study, two different RCAS-shNf1 (GR249 and GF249) and shp53 (R696 and mR696) was used for the generation of the murine brain tumors. Each RCAS vector has different structure but the target sequence against the Nf1 and p53 is same and similar knockdown effect was observed. Tumor grade were determined with the residual sections after a piece of tumor tissue were excised for the RNA extraction. The detail information of the experiment was described in the associated-publication. Murine_shere: Murine neurosphere lines were generated by a retroviral infection with the relevant RCAS viruses. The total RNAs were obtained from the murine neurosphere lines expressing the RCAS-shGL2, shNf1, shp53 or shNf1+shp53 and the gene expression profiles of the shNf1, shp53 or shNf1/p53 cells were then compared to the control shGL2 cells.
2014-04-03 | E-GEOD-45874 | biostudies-arrayexpress
Project description:Tamoxifen was administered to Glast-CreER;Nf1-flox/flox;Tp53-flox/flox or Glast-CreER;Ascl1-flox/flox;Nf1-flox/flox;Tp53-flox/flox at E14.5 to induce tumors in the brain
2020-11-05 | GSE152400 | GEO
Project description:CRISPR-edited human induced pluripotent stem cell (iPSC)-derived glioma models provide a robust platform to investigate the biology of these aggressive tumors in an isogenic background or to test possible treatments in preclinical settings. We created iPSC12 lines that carry different combinations of glioma driver mutations using CRISPR/Cas9 genome editing technology, including TP53-/-, ATRX-/-, IDH1-R132H/WT, PTEN-/-, CDKN2A/B-/-, TERT promoter(TERTp) C228T/WT, MTAP-/-, and overexpression (OE) of EGFRvIII oncogenic isoform. Edited iPSCs were then differentiated into neural progenitor cells (NPC) using a small molecule protocol. We cultured the edited NPCs in 3D organoid with an FBS-containing differentiation medium. After 14 days, different genotypes of NPCs formed organoids were harvest and RNAs were isolated and subjected to RNA-seq analysis. To create an in vivo model system, NPCs with different genotypes were intracranially transplanted into athymic mice. Mice were sacrificed when pathologic symptoms developed resulting from tumor burden or 120 days post brain transplantation. RNAs were extracted from the tumor region of brain tissue sections and subjected to RNA-seq analysis. Our study showed that the iPSC-based model of gliomas displayed distinct mutation-dependent variation in transcriptome, which recapitulated the gene expression signatures of human gliomas.
2024-05-15 | GSE212671 | GEO
Project description:Solid cancers develop within a supportive microenvironment that promotes tumor formation and continued growth through the elaboration of mitogens and chemokines. Within these tumors, monocytes (macrophages and microglia) represent rich sources of these stromal factors. Leveraging a genetically-engineered mouse model of neurofibromatosis type 1 (NF1) low-grade brain tumor (optic glioma), previous studies have demonstrated that microglia are important for glioma formation and maintenance. To identify the tumor-associated microglial factors that support glioma growth (gliomagens), we employed a comprehensive large scale discovery effort using optimized advanced RNA-sequencing methods. Candidate gliomagens were prioritized to identify potential secreted or membrane-bound proteins, which were next validated by quantitative RT-PCR and RNA FISH following minocycline-mediated microglial inactivation in vivo. Using these selection criteria, Ccl5 was identified as a highly expressed chemokine in both genetically engineered Nf1 mouse and human optic gliomas. As a candidate gliomagen, recombinant Ccl5 increased Nf1-deficient optic nerve astrocyte growth in vitro. Importantly, consistent with its critical role in maintaining tumor growth, Ccl5 inhibition with neutralizing antibodies reduced Nf1 mouse optic glioma growth in vivo. Collectively, these findings establish Ccl5 as critical stromal growth factor in low-grade glioma maintenance relevant to future microglia-targeted therapies for brain tumors.
2016-08-17 | GSE65831 | GEO