MiRNA profiling of adult Mouse Grey Matter versus GFAP-HaV12-Ras Astrocytoma (tumor)
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PROVIDER: PRJNA545737 | ENA |
REPOSITORIES: ENA
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Project description:The goal of the experiment was to determine global miRNA expression in adult mouse neocortex versus mouse astrocytoma tissue (GFAP-HaV12-Ras)
2019-06-30 | GSE132052 | GEO
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.
2017-07-03 | GSE74567 | 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 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
Project description:Multiple sclerosis cortical normal-appearing grey matter, grey matter lesions, and control grey matter
| PRJNA543111 | ENA
Project description:Multiple sclerosis cortical normal-appearing grey matter and grey matter lesions
| PRJNA543112 | ENA
Project description:Multiple sclerosis cortical normal-appearing grey matter and control grey matter
| PRJNA543114 | ENA
Project description:Microglia are brain-resident, myelin-phagocytosing cells, yet their role in lesion initiation in grey and white matter regions in multiple sclerosis (MS) is unclear. We isolated primary microglia from both, occipital cortex and corpus callosum, of 10 MS and 11 control donors and studied their transcriptional profile by RNA sequencing, thereby identifying regional and MS-associated changes. Identification of pathways underlying regional differences showed a relatively increased type I interferon response in cortical grey matter microglia, while white matter microglia more highly expressed NF-κB pathway genes. In normal-appearing white matter MS tissue, lipid metabolism genes were increased, suggesting processing of myelin by microglia already in areas seemingly devoid of MS pathology. Normal-appearing grey matter MS microglia showed increased activation of glycolysis and metal ion homeostasis, possibly reflecting microglia reacting to iron depositions. Notably, expression of genes associated with microglia homeostasis were hardly changed, suggesting that subtle regional changes in MS-associated microglia do not yet affect their resting state.
2019-03-13 | GSE111972 | GEO
Project description:Periventricular heterotopia (PH), the most common form of grey matter heterotopia, represents a cortical malformation that is often associated with developmental delay and drug-resistant seizures1,2. The detailed neurophysiological underpinnings of PH symptoms in humans remain, however, elusive. Human cerebral organoids (hCOs) derived from patients with causative mutations in FAT4 or DCHS1 exhibit key features of PH3, but neuronal activity in these 3D models has not yet been investigated. Here, using silicon probe recordings, we detected exaggerated spontaneous spike activity in FAT4 and DCHS1 hCOs, suggesting functional changes in neuronal networks. Patch-clamp recordings revealed a decreased spike threshold exclusively for DCHS1 neurons, which presumably results from an enhanced density of somatic voltage-gated sodium channels. Furthermore, single-cell morphological reconstructions and immunostainings demonstrated greater morphological complexity of neurons and synaptic alterations, rather than an imbalance of excitatory-inhibitory neuron number, as contributing to the hyperactivity observed in FAT4 and DCHS1 hCOs. The morphological phenotype was rescued by an expression of wild-type DCHS1 in DCHS1 neurons. In addition, transcriptome and proteome analyses uncovered changes in GO terms associated with neuronal morphology and synaptic function. Overall, we provide detailed new insights into cellular alterations likely contributing to the emergence of symptoms in grey matter heterotopia.
2025-01-02 | GSE220673 | GEO