Adverse prognosis of glioblastoma contacting the subventricular zone: biological correlates
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE134783 | GEO | 2019/07/25
REPOSITORIES: GEO
Similar Datasets
Project description: Not available
| S-EPMC6788733 | biostudies-literature
Project description:Adverse prognosis of glioblastoma contacting the subventricular zone: biological correlates
| PRJNA556417 | ENA
Project description:Background: The spatial relationship of glioblastoma (GBM) to the subventricular zone (SVZ) is associated with inferior patient survival. However, the underlying molecular phenotype is largely unknown. We interrogated an SVZ-dependent transcriptome and potential location-specific prognostic markers. Methods: mRNA microarray data of a discovery set (n = 36 GBMs) were analyzed for SVZ-dependent gene expression and process networks using the MetaCoreTM workflow. Differential gene expression was confirmed by qPCR in a validation set of 142 IDH1 wild-type GBMs that was also used for survival analysis. Results: Microarray analysis revealed a transcriptome distinctive of SVZ+ GBM that was enriched for genes associated with Notch signaling. No overlap was found to The Cancer Genome Atlas’s molecular subtypes. Independent validation of SVZ-dependent expression confirmed four genes with simultaneous prognostic impact: overexpression of HES4 (p = 0.034; HR 1.55) and DLL3 (p = 0.017; HR 1.61) predicted inferior, and overexpression of NTRK2 (p = 0.049; HR 0.66) and PIR (p = 0.025; HR 0.62) superior overall survival (OS). Additionally, overexpression of DLL3 was predictive of shorter progression-free survival (PFS) (p = 0.043; HR 1.64). Multivariate analysis revealed overexpression of HES4 to be independently associated with inferior OS (p = 0.033; HR 2.03), and overexpression of DLL3 with inferior PFS (p = 0.046; HR 1.65). Conclusions: We identified four genes with SVZ-dependent expression and prognostic significance, among those HES4 and DLL3 as part of Notch signaling, suggesting further evaluation of location-tailored targeted therapies.
2016-10-26 | GSE83537 | GEO
Project description:Transcriptional profiling of subventricular zone (SVZ) progenitors comparing control healthy mice to mice induced to develop an autoimmune demyelination (EAE model). Goal was to unveil genes involved in demyelination-induced reactivity of SVZ progenitors. Two-condition experiment, healthy vs. EAE derived SVZ progenitors. Biological replicates: 2 control replicates, 2 EAE replicates. SVZ progenitors were sorted in two cell populations: neuronal progenitors (PSA-NCAM magnetic sorting) and glial progenitors (NG2 magnetic sorting). Progenitors from healthy mice are reference samples.
2013-09-09 | E-GEOD-47486 | biostudies-arrayexpress
Project description:Transcriptional profiling of subventricular zone (SVZ) progenitors comparing control healthy mice to mice induced to develop an autoimmune demyelination (EAE model). Goal was to unveil genes involved in demyelination-induced reactivity of SVZ progenitors.
2013-09-09 | GSE47486 | GEO
Project description:Histone 3 lysine 4 trimethylation (H3K4me3) is known to be associated with transcriptionally active or poised genes and required for postnatal neurogenesis within the subventricular zone (SVZ) in the rodent model. Previous comparisons have shown significant correlation between baboon (Papio anubis) and human brain. In this study, we demonstrate that chromatin activation mark H3K4me3 is present in undifferentiated progenitor cells within the SVZ of adult baboon brain. To identify the targets and regulatory role of H3K4me3 within the baboon SVZ, we developed a technique to purify undifferentiated SVZ cells while preserving the endogenous nature without introducing culture artifact to maintain the in vivo chromatin state for genome-wide studies (ChIP-Seq and RNA-Seq). We identified that H3K4me3 is significantly enriched for genes involved in cell cycle, cell signaling, nervous system development, metabolism, and ribosomal biogenesis. Among these genes, RNA-Seq identified that genes associated with cellular signaling/maintenance, DNA replication, metabolism, and protein synthesis are expressed. We found that 72% of H3K4me3-enriched genes in undifferentiated SVZ cells are expressed (1913 genes are detectable by RNA-Seq; 2663 genes enriched with H3K4me3 by ChIP-Seq). On the other hand, 750 out of total 2663 H3K4me3-enriched genes are not detectable by RNA-Seq, suggesting 28% of genes in SVZ are poised for activation.
2014-07-16 | GSE58527 | GEO
Project description:Histone 3 lysine 4 trimethylation (H3K4me3) is known to be associated with transcriptionally active or poised genes and required for postnatal neurogenesis within the subventricular zone (SVZ) in the rodent model. Previous comparisons have shown significant correlation between baboon (Papio anubis) and human brain. In this study, we demonstrate that chromatin activation mark H3K4me3 is present in undifferentiated progenitor cells within the SVZ of adult baboon brain. To identify the targets and regulatory role of H3K4me3 within the baboon SVZ, we developed a technique to purify undifferentiated SVZ cells while preserving the endogenous nature without introducing culture artifact to maintain the in vivo chromatin state for genome-wide studies (ChIP-Seq and RNA-Seq). We identified that H3K4me3 is significantly enriched for genes involved in cell cycle, cell signaling, nervous system development, metabolism, and ribosomal biogenesis. Among these genes, RNA-Seq identified that genes associated with cellular signaling/maintenance, DNA replication, metabolism, and protein synthesis are expressed. We found that 72% of H3K4me3-enriched genes in undifferentiated SVZ cells are expressed (1913 genes are detectable by RNA-Seq; 2663 genes enriched with H3K4me3 by ChIP-Seq). On the other hand, 750 out of total 2663 H3K4me3-enriched genes are not detectable by RNA-Seq, suggesting 28% of genes in SVZ are poised for activation. RNA-seq profiles were generated from adult baboon subventricular zone primary cells by paired-end deep sequencing with an Illumina HiSeq 2000. RNA-Seq Analysis: Total RNA was extracted from purified baboon SVZ cells using TRIzol reagent, and sequencing libraries were generated with the Illumina RNA-Seq library kit. Paired-end RNA-deepSeq (76 base pair; >300 million tag reads; 269,081,636 mapped reads) were aligned to hg19. DESeq was used to normalize raw read counts, and Cufflink reports read counts and estimated FPKM (fragments per kilobase of exon per million fragments mapped; http://cufflinks.cbcb.umd.edu/faq.html#fpkm). Genes with expression values >1 FPKM were considered for subsequent analyses.
2014-07-16 | E-GEOD-58527 | biostudies-arrayexpress
Project description:The lateral ventricle subventricular zone (SVZ) is a frequent and consequential site of pediatric and adult glioma spread, but the cellular and molecular mechanisms mediating this are poorly understood. We demonstrate that neural precursor cell (NPC):glioma cell communication underpins this propensity of glioma to colonize the SVZ through secretion of chemoattractant signals toward which glioma cells home. Biochemical, proteomic, and functional analyses of SVZ NPC-secreted factors revealed the neurite outgrowth-promoting factor pleiotrophin, along with required binding partners SPARC/SPARCL1 and HSP90B, as key mediators of this chemoattractant effect. Pleiotrophin expression is strongly enriched in the SVZ, and pleiotrophin knockdown starkly reduced glioma invasion of the SVZ in the murine brain. Pleiotrophin, in complex with the binding partners and signaling through the receptor PTPRZ1, activated glioma Rho/ROCK signaling, and ROCK inhibition decreased invasion toward SVZ NPC-secreted factors. These findings demonstrate a pathogenic role for NPC:glioma interactions and potential therapeutic targets to limit glioma invasion.
2017-07-26 | GSE99812 | GEO
Project description:We performed large-scale single cell profiling of dissociated V-SVZ and OB cells from the same animal carrying either the hGFAP::CreERT2; Rosa26LSL-TdTomato (GCERT2) reporter, or ratNes::FLPOER; Rosa26FSF-TdTomato (NesFLPO) reporter. Scope-Seq profiling was performed on dissociated V-SVZ cells from C57BL/6J animals.
2020-06-21 | GSE134918 | GEO
Project description:Throughout postnatal life in mammals, neural stem cells (NSCs) are located in the subventricular zone (SVZ) of the lateral ventricles. The greatest diversity of neuronal and glial lineages they generate occurs during early postnatal life in a region-specific manner. In order to evaluate potential heterogeneity in the NSC pool, we microdissected the dorsal and lateral SVZ at different postnatal ages and isolated NSCs and their immediate progeny based on their expression of Hes5-EGFP/Prominin1 and Ascl1-EGFP, respectively. Whole genome comparative transcriptome analysis revealed transcriptional regulators as major hallmarks that sustain postnatal SVZ regionalization. Manipulation of single genes encoding for locally enriched transcription factors influenced NSC specification indicating that the fate of regionalized postnatal SVZ NSCs can be readily modified . These findings reveal functional heterogeneity of NSCs in the postnatal SVZ and provide targets to recruit region-specific lineages in regenerative contexts. Microarrays of neural stem cells, early progenitors and the tissue from subregions of the subventricular zone were compiled to screen for the full extent of heterogeneity in this region during postnatal life. Spatially distinct regions of the developing forebrain subventricular zone (SVZ) aged at P4, P8 and P11 were microdissected in RNAse free/sterile conditions. Mice expressing Ascl1-EGFP in the SVZ were used to aid accurate microdissection of the dorsal and lateral wall of each of the studied time points as per our previous publications characterizing this method. As well as at the whole microdomain level, additionally, NSCs (Hes5-EGFP+/Prom1+) and early progenitors (Ascl1-EGFP+) from each microdomain were further isolated by FAC sorting methods. This was to provide a comprehensive gene expression analysis at the tissue level and at the cellular level. Generally, 1 litter was used to yield 1 'n' number of replicates. A total of 23 affymetrix analysis were performed.
2015-04-07 | E-GEOD-60905 | biostudies-arrayexpress