Differential Expression Studies in Murine Splenic Cells During Prion Infection
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE17446 | GEO | 2011/07/01
SECONDARY ACCESSION(S): PRJNA118871
REPOSITORIES: GEO
Similar Datasets
Project description:DNA microarrays were used to profile gene expression in normal murine splenic cells vs. prion infected splenic cells with the aim of identifying host factors involved in prion propagation and/or useful as biomarkers for early diagnosis. Two condition experiment, prion infected murine splenic cells vs. normal murine splenic cells: 4 infected biological replicates, 2 control biological replicates, 2 technical replicates (dye-swaps) for each competitive hybridization. Samples were run on 4 different arrays: MPB Murine 16K BMAP-MSV printrun 7.1 microarray MPB Murine 16K BMAP-MSV printrun 9.1 microarray MPB Murine 32K Oligo printrun 4.1 microarray Agilent 4x44K Whole Mouse Genome
2011-07-01 | E-GEOD-17446 | biostudies-arrayexpress
Project description:Prions consist of aggregates of abnormal conformers of cellular prion protein (PrPC). They propagate by recruiting host-encoded PrPC although the critical interacting proteins and the reasons for the differences in susceptibility of distinct cell lines and populations are unknown. We derived a lineage of cell lines with markedly differing susceptibilities, unexplained by PrPC expression differences, to identify such factors. We examined the transcriptomes of prion-resistant revertants, isolated from highly susceptible cells, and identified a gene expression signature associated with susceptibility. Several of these genes encode proteins with a role in extracellular matrix (ECM) remodelling, a compartment in which disease-related PrP deposits. Loss-of-function of nine of these genes significantly increased susceptibility. Remarkably, inhibition of fibronectin 1 binding to integrin α8 by RGD peptide inhibited metalloproteinases (MMP)-2/9 whilst increasing prion propagation rates. This indicates that prion replication may be controlled by MMPs at the ECM in an integrin-dependent manner.
2014-07-31 | GSE56275 | GEO
Project description:Mammalian prion diseases are fatal and transmissible neurological conditions caused by the propagation of prions, self-replicating multimeric assemblies of misfolded forms of host cellular prion protein. Despite extensive studies investigating the changes in transcriptional profiles in prion diseases the mechanisms by which prion diseases induce cellular toxicity, including changes in gene expression profiles are yet to be fully characterized. Here, we took advantage of the recent developments in single-cell technologies and performed an unbiased whole-transcriptome single-nucleus transcriptomic analysis in prion disease.
2023-01-31 | GSE214374 | GEO
Project description:Mammalian prion diseases are fatal and transmissible neurological conditions caused by the propagation of prions, self-replicating multimeric assemblies of misfolded forms of host cellular prion protein. Despite extensive studies investigating the changes in transcriptional profiles in prion diseases the mechanisms by which prion diseases induce cellular toxicity, including changes in gene expression profiles are yet to be fully characterized. Here, we took advantage of the recent developments in single-cell technologies and performed an unbiased whole-transcriptome single-nucleus transcriptomic analysis in prion disease.
2023-01-31 | GSE214375 | GEO
Project description:Mammalian prion diseases are fatal and transmissible neurological conditions caused by the propagation of prions, self-replicating multimeric assemblies of misfolded forms of host cellular prion protein. Despite extensive studies investigating the changes in transcriptional profiles in prion diseases the mechanisms by which prion diseases induce cellular toxicity, including changes in gene expression profiles are yet to be fully characterized. Here, we took advantage of the recent developments in single-cell technologies and performed an unbiased whole-transcriptome single-nucleus transcriptomic analysis in prion disease.
2023-01-31 | GSE214373 | GEO
Project description:This report describes our study of the efficacy and the potential mechanism underlying the anti-prion action of a new anti-prion compound having a glycoside structure in prion-infected cells. The study revealed involvements of two factors in the mechanism of the compound action: interferon and a microtubule nucleation activator, phosphodiesterase 4D interacting protein. In particular, phosphodiesterase 4D interacting protein was suggested to be important in regulating the trafficking or fusion of prion protein-containing vesicles or structures in cells. The findings of the study are expected to be useful not only for the elucidation of cellular regulatory mechanisms of prion protein, but also for the implication of new targets for therapeutic development.
2014-02-22 | GSE55241 | GEO
Project description:This report describes our study of the efficacy and the potential mechanism underlying the anti-prion action of a new anti-prion compound having a glycoside structure in prion-infected cells. The study revealed involvements of two factors in the mechanism of the compound action: interferon and a microtubule nucleation activator, phosphodiesterase 4D interacting protein. In particular, phosphodiesterase 4D interacting protein was suggested to be important in regulating the trafficking or fusion of prion protein-containing vesicles or structures in cells. The findings of the study are expected to be useful not only for the elucidation of cellular regulatory mechanisms of prion protein, but also for the implication of new targets for therapeutic development. Prion-infected N167 cells were treated with either anti-prion glycoside compound (Gly-9) or control glycoside compound (Gly-14) at a dose of 5 M-NM-<g/mL for three days. Then, gene expression profiles were analyzed by DNA microarray analysis. Experiments were performed in quadruplicate.
2014-02-22 | E-GEOD-55241 | biostudies-arrayexpress
Project description:Cell culture models allow prion propagation studies ex vivo after contact with infectious brain homogenates. To date, among the neural cell lines, the mouse neuroblastoma-derived cell line N2a has been one of the most widely used model and has yet provided interesting insights into cell biology of prion propagation. Remarkably, persistently-infected N2a sublines have been set up and replicate prions without exhibiting any pathological changes. One further interesting feature of N2a is the possibility to establish by subcloning, sublines with a range of susceptibility to prions. Indeed, susceptible sublines propagate prions and accumulate the pathogenic isoform of the prion protein, PrPSc, at the opposite of resistant sublines. The aim of our study was to apply large-scale expression analysis using microarrays combined with quantitative real-time PCR to examine the gene expression profile in a persistently-infected N2a cell line, N2a58, infected with the mouse-adapted prion strain 22L, to seek for prion-specific gene transcription. We also questioned if we could observe identical variations of expression of these genes in three other 22L-infected N2a sublines. Finally, we examined the transcriptional state of a N2a subline considered as resistant when exposed to prions. Common pathways of gene transcription would disclose information on the molecular basis of the cell infection and help to identify potential therapeutic targets. Keywords: other
2009-07-07 | GSE5844 | GEO
Project description:Affymetrix genechip profiling analsysis (MOE430A and MOE430B) of murine neuroblastoma cells infected with either RML prion strain or mock brain homogenate Keywords: Affymetrix gene expression profiling
2008-02-25 | GSE7229 | GEO
Project description:Prion diseases are fatal transmissible neurodegenerative conditions of humans and animals that arise through neurotoxicity induced by PrP misfolding. The cellular and molecular mechanisms of prion-induced neurotoxicity remain undefined. Understanding these processes will underpin therapeutic and control strategies for human and animal prion diseases, respectively. Prion diseases are difficult to study in their natural hosts and require the use of tractable animal models. Here we used RNA-Seq-based transcriptome analysis of prion-exposed Drosophila to probe the mechanism of prion-induced neurotoxicity. Adult Drosophila transgenic for pan neuronal expression of ovine PrP targeted to the plasma membrane exhibit a neurotoxic phenotype evidenced by decreased locomotor activity after exposure to ovine prions at the larval stage. Pathway analysis and quantitative PCR of genes differentially expressed in prion-infected Drosophila revealed up-regulation of cell cycle activity and DNA damage response, followed by down-regulation of eIF2 and mTOR signalling. Mitochondrial dysfunction was identified as the principal toxicity pathway in prion-exposed PrP transgenic Drosophila. The transcriptomic changes we observed were specific to PrP targeted to the plasma membrane since these prion-induced gene expression changes were not evident in similarly-treated Drosophila transgenic for cytosolic pan neuronal PrP expression, or in non-transgenic control flies. Collectively, our data indicate that aberrant cell cycle activity, repression of protein synthesis and altered mitochondrial function are key events involved in prion-induced neurotoxicity, and correlate with those identified in mammalian hosts undergoing prion disease. These studies highlight the use of PrP transgenic Drosophila as a genetically well-defined tractable host to study mammalian prion biology.
2020-01-31 | GSE144028 | GEO