MiRNA profiling of adult Mouse Grey Matter versus GFAP-HaV12-Ras Astrocytoma (tumor)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE132052 | GEO | 2019/06/30
REPOSITORIES: GEO
Similar Datasets
Project description:MiRNA profiling of adult Mouse Grey Matter versus GFAP-HaV12-Ras Astrocytoma (tumor)
| PRJNA545737 | ENA
Project description:Modulation of the GFAP cytoskeleton in astrocytoma cells alters processes involved in extracellular matrix remodelling and cell-cell signalling – a transcriptome analysis Astrocytomas grade IV are malignant brain tumours with no effective treatment and a five year survival rate of only 5%. Expression of Glial Fibrillary Acidic Protein (GFAP) is lower in high astrocytoma grade, but the expression of the splice isoform GFAPδ is similar in low and high-grade astrocytomas. Thus the ratio of GFAPδ/α is increased in high-grade astrocytomas. We studied transcriptome changes in astrocytoma cell lines resulting from an induced alteration of GFAP isoform expression. GFAPα or GFAPδ were increased or decreased by recombinant expression or shRNA mediated knockdown of GFAPpan or GFAPα. We find that the most prominent effects are induced by the modulations where the GFAPδ/GFAPα ratio is increased. Gene ontology analysis revealed that the main effects of GFAP modulation take place in the extracellular matrix remodelling and cellular signalling clusters, with possible implications in astrocytoma invasive behaviour and angiogenesis.
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2020-01-13 | GSE131282 | GEO
Project description:Olfactory bulb transcript levels for GFAP transgenic mice compared to wildtype at 3wks and 4mos Keywords = GFAP Keywords = Rosenthal fibers Keywords = Alexander disease Keywords: other
2005-07-20 | GSE977 | GEO
Project description:Tumors of the central nervous system are the most common solid neoplasia during human childhood, representing one of the leading causes of cancer-related mortality. Tumors that originate from astrocyte cells (astrocytoma) in the brain are the most frequently found. According to their histological and pathological features, these tumors are classified into four categories. However, recently an extra layer of molecular classification of the tumorigenesis-associated genes IDH1/2 and H3F3A has been incorporated into the classification guidelines. While mutations in H3F3A are exclusively found in a subtype of pediatric astrocytoma grade IV, mutations in IDH1/2 are very rare in children younger than 14 years old. The transcriptomic profiles of astrocytoma in adults and children have been extensively studied however focusing on the study of the transcriptomic profile of the different grades of astrocytoma (including the additional layer of molecular classification) in pediatric populations are scarce. Therefore, we have profiled the transcriptomic landscape of the four grades of pediatric astrocytoma by RNA sequencing.
2022-10-25 | GSE196694 | GEO
Project description:Astrocytomas are the most common malignant brain tumours and are to date incurable. It is unclear how astrocytomas progress into higher malignant grades. The intermediate filament cytoskeleton is emerging as an important regulator of malignancy in several tumours. The majority of the astrocytomas express the intermediate filament protein Glial Fibrillary Acidic Protein (GFAP). Several GFAP splice variants have been identified and the main variants expressed in human astrocytoma are the GFAP? and GFAP? isoforms. Here we show a significant downregulation of GFAP? in grade IV astrocytoma compared to grade II and III, resulting in an increased GFAP?/? ratio. Mimicking this increase in GFAP?/? ratio in astrocytoma cell lines and comparing the subsequent transcriptomic changes with the changes in the patient tumours, we have identified a set of GFAP?/? ratio-regulated high-malignant and low-malignant genes. These genes are involved in cell proliferation and protein phosphorylation, and their expression correlated with patient survival. We additionally show that changing the ratio of GFAP?/?, by targeting GFAP expression, affected expression of high-malignant genes. Our data imply that regulating GFAP expression and splicing are novel therapeutic targets that need to be considered as a treatment for astrocytoma.
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Project description:In the present study, we applied a quantitative MS-based strategy to characterize the proteome and phosphoproteome in HRAS- or IDH1-driven glioma cells. We describe the driving roles of the MEK and PI3K signaling pathways in RAS-NHA cells, and uncover oncogenic signaling in other pathways. We highlight the interplay between the signaling cascades and show that inhibition of MEK and PI3K reverses phosphorylation signaling patterns driven by oncogenic RAS overexpression. Applying a histone hybrid chemical labeling method and high-resolution MS, we identified significant histone methylation, acetylation, and butyrylation changes in IDH1mut-NHA cells. Our results suggest a global transcriptional repressive state, consistent with the down-regulation of the proteome, transcriptome, and the DNA hyper-methylated state in IDH1mut-NHA cells. We provide a unique resource of altered proteins, phosphosites, and histone PTMs in RAS and IDH1 mutant astrocytoma cell lines, providing insight into oncogenesis in glioma beyond the transcriptomic level.
2016-12-23 | PXD004945 | Pride
Project description:Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the brain. Among characteristics of MS pathology are cortical grey matter abnormalities, which have been linked to clinical signs such as cognitive impairment. To understand MS cortical grey matter pathogenesis, we performed differential gene expression analysis of MS normal appearing grey matter (NAGM) and control grey matter. HLA-DRB1 is the transcript with highest expression in MS NAGM with a bimodal distribution among the examined cases. Genotyping revealed that every case with the MS-associated HLA-DR15 haplotype also shows high HLA-DRB1 expression. Quantitative immunohistochemical analysis confirmed the higher expression of HLA-DRB1 in HLA-DRB1*15:01 cases at the protein level. Analysis of grey matter lesion size revealed a significant increase of cortical lesion size in cases with high HLA-DRB1 expression. Our data indicate that increased HLA-DRB1 expression in the brain of MS patients may be an important factor in how the HLA-DR15 haplotype contributes to MS risk in the target organ.
2020-01-13 | GSE131281 | GEO
Project description:Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the brain. Among characteristics of MS pathology are cortical grey matter abnormalities, which have been linked to clinical signs such as cognitive impairment. To understand MS cortical grey matter lesion pathogenesis, we performed differential gene expression analysis of MS cortical normal-appearing grey matter (NAGM) and grey matter lesions. HLA-DRB1 is the transcript with highest expression in MS NAGM with a bimodal distribution among the examined cases. Genotyping revealed that every case with the MS-associated HLA-DR15 haplotype also shows high HLA-DRB1 expression. Quantitative immunohistochemical analysis confirmed the higher expression of HLA-DRB1 in HLA-DRB1*15:01 cases at the protein level. Analysis of grey matter lesion size revealed a significant increase of cortical lesion size in cases with high HLA-DRB1 expression. Our data indicate that increased HLA-DRB1 expression in the brain of MS patients may be an important factor in how the HLA-DR15 haplotype contributes to MS risk in the target organ.
2020-01-13 | GSE131279 | GEO
Project description:Increasing evidence indicates heterogeneity in functional and molecular properties of oligodendrocyte lineage cells both during development and under pathologic conditions. In multiple sclerosis, remyelination of grey matter lesions exceeds that in white matter. Here we used cells derived from grey matter versus white matter regions of surgically resected human brain tissue samples, to compare the capacities of human A2B5-positive progenitor cells and mature oligodendrocytes to ensheath synthetic nanofibers, and relate differences to the molecular profiles of these cells. For both cell types, the percentage of ensheathing cells was greater for grey matter versus white matter cells. For both grey matter and white matter samples, the percentage of cells ensheathing nanofibers was greater for A2B5-positive cells versus mature oligodendrocytes. Grey matter A2B5-positive cells were more susceptible than white matter A2B5-positive cells to injury induced by metabolic insults. Bulk RNA sequencing indicated that separation by cell type (A2B5-positive vs mature oligodendrocytes) is more significant than by region but segregation for each cell type by region is apparent. Molecular features of grey matter versus white matter derived A2B5-positive and mature oligodendrocytes were lower expression of mature oligodendrocyte genes and increased expression of early oligodendrocyte lineage genes. Genes and pathways with increased expression in grey matter derived cells with relevance for myelination included those related to responses to external environment, cell-cell communication, cell migration, and cell adhesion. Immune and cell death related genes were up-regulated in grey matter derived cells. We observed a significant number of up-regulated genes shared between the stress/injury and myelination processes, providing a basis for these features. In contrast to oligodendrocyte lineage cells, no functional or molecular heterogeneity was detected in microglia maintained in vitro, likely reflecting the plasticity of these cells ex vivo. The combined functional and molecular data indicate that grey matter human oligodendrocytes have increased intrinsic capacity to myelinate but also increased injury susceptibility, in part reflecting their being at a stage earlier in the oligodendrocyte lineage.
2024-11-08 | GSE281006 | GEO