Transcriptome analysis of peripheral lymphoid tissue immediately before and after the detection of PrPSc in sheep scrapie
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ABSTRACT:
ORGANISM(S): Ovis aries
SUBMITTER: Anton Gossner
PROVIDER: E-MTAB-2327 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Sheep scrapie is a transmissible spongiform encephalopathy (TSE), which are invariably fatal neurodegenerative diseases of the central nervous system (CNS). Accumulation of the misfolded prion protein, PrPSc in the CNS results in progressive neurodegenerative disease. For many transmissible spongiform encephalopathies (TSEs), peripheral lymphoid tissue is an important site of PrPSc amplification but without obvious immunological consequence. Susceptible VRQ homozygous New Zealand Cheviot sheep were infected with SSBP/1 scrapie by inoculation in the drainage area of the prescapular lymph nodes. PrPSc was consistently detected by immunohistology in these nodes at 50 days post infection (dpi). This study compares the genes and physiological pathways that are affected by the progression of TSE disease in the prescapular lymph nodes, focussing on time points immediately before (10 dpi) and after (50 dpi) the detection of disease-associated PrPSc.
2014-04-06 | E-MTAB-2330 | biostudies-arrayexpress
Project description:Sheep scrapie is a transmissible spongiform encephalopathy (TSE), which are invariably fatalM- neurodegenerative diseases of the central nervous system (CNS). Accumulation of the misfolded prion protein, PrPSc in the CNS results in progressive neurodegenerative disease. Susceptible VRQ homozygous New Zealand Cheviot sheep were infected with standard scrapie sheep prion (SSBP/1) scrapie by inoculation in the drainage area of the prescapular lymph nodes. PrPSc was consistently detected by immunohistology in the CNS at XX days post infection (dpi). This study compares the genes and physiological pathways that are affected by the progression of TSE disease in the CNS, focusing on time points immediately before (XX dpi) and after (XX dpi) the detection of disease-associated PrPSc.
2014-06-01 | E-MTAB-2369 | biostudies-arrayexpress
Project description:Sheep scrapie is a transmissible spongiform encephalopathy (TSE), which are invariably fatal neurodegenerative diseases of the central nervous system (CNS). Accumulation of the misfolded prion protein, PrPSc in the CNS results in progressive neurodegenerative disease. Susceptible VRQ homozygous New Zealand Cheviot sheep were infected with SSBP/1 scrapie by inoculation in the drainage area of the prescapular lymph nodes. PrPSc was consistently detected by immunohistology in the CNS at 125 days post infection (dpi). This study compares the genes and physiological pathways that are affected by the progression of TSE disease in the CNS, focusing on time points immediately before (75dpi) and at the time point when PrPSc is consistently detected in the CNS (125 dpi).
2014-06-01 | E-MTAB-2385 | biostudies-arrayexpress
Project description:Sheep scrapie (Sc) is the classical transmissible spongiform encephalopathy (prion disease). The conversion of normal cellular prion protein (PrPC) to disease-associated prion protein (PrPSc) is a fundamental component of prion disease pathogenesis. The molecular mechanisms contributing to prion diseases and the impact of PrPSc accumulation on cellular biology are not fully understood. To define the molecular changes associated with PrPSc accumulation, primary sheep microglia were inoculated with PrPSc and then the transcriptional profile of these PrPSc-accumulating microglial cells was compared to the profile of PrPSc-lacking microglial cells using the Affymetrix Bovine Genome Array. The experimental design included three biological replicates, each with three technical replicates, and samples that were collected at the point of maximal PrPSc accumulation levels as measured by ELISA. The array analysis revealed 19 upregulated genes and 30 downregulated genes in PrPSc-accumulating microglia. Three transcripts (CCL2, SGK1, and AASDHPPT) were differentially regulated in a direction similar to previous reports from mouse or human models, whereas the response of three other transcripts (MT1E, NR4A1, PKP2) conflicted with previous reports. Overall, the results demonstrated a limited transcriptional response to PrPSc accumulation, when compared to microglia and macrophage cultures infected with other agents such as viruses and bacteria. This is the first microarray-based analysis of prion accumulation in primary cells derived from a natural TSE-host. Keywords: disease state analysis
2008-09-06 | GSE12688 | GEO
Project description:Scrapie is a Transmissible Spongiform Encephalopathy (TSE) that affects sheep and goats and it is considered a good natural animal model to study prion diseases. Although changes in DNA methylation occur in many neurodegenerative diseases including human prion diseases, potential DNA methylation alterations have not yet been investigated in the central nervous system (CNS) of any prion disease models or naturally infected cases. We present here a whole genome bisulfite sequencing analysis (WGBS) from thalamus of four naturally scrapie infected sheep and four controls. All animals were female, carried the ARQ/ARQ genotype for the PRNP allele and were sacrificed at similar age (4 to 6 years old). Even if genomes displayed similar average methylation levels, we identified 39 differentially methylated promoters (DMP) and a total of 8,907 differentially methylated regions (DMR). Gene Ontology enrichment revealed that hypomethylated DMRs were enriched in genes involved in transmembrane transport and cell adhesion whereas hypermethylated DMRs were related with intracellular signal transduction genes. Moreover, we compared the set of identified DMRs with genes previously described to be differentially expressed in scrapie and with a set of genes encoding proteins defined to be tenfold more abundant in specific types of CNS cells finding that some of these genes also harboured DMRs. Finally, a validation study using qPCR was conducted showing differences in the expression of five genes (PCDH19, SNCG, WDR45B, PEX1 and CABIN1) that matched the methylation changes observed in the genomic study. Altogether, these findings suggest a potential regulatory role of CNS DNA methylation in prion diseases.
2022-03-10 | GSE184767 | GEO
Project description:Sheep scrapie (Sc) is the classical transmissible spongiform encephalopathy (prion disease). The conversion of normal cellular prion protein (PrPC) to disease-associated prion protein (PrPSc) is a fundamental component of prion disease pathogenesis. The molecular mechanisms contributing to prion diseases and the impact of PrPSc accumulation on cellular biology are not fully understood. To define the molecular changes associated with PrPSc accumulation, primary sheep microglia were inoculated with PrPSc and then the transcriptional profile of these PrPSc-accumulating microglial cells was compared to the profile of PrPSc-lacking microglial cells using the Affymetrix Bovine Genome Array. The experimental design included three biological replicates, each with three technical replicates, and samples that were collected at the point of maximal PrPSc accumulation levels as measured by ELISA. The array analysis revealed 19 upregulated genes and 30 downregulated genes in PrPSc-accumulating microglia. Three transcripts (CCL2, SGK1, and AASDHPPT) were differentially regulated in a direction similar to previous reports from mouse or human models, whereas the response of three other transcripts (MT1E, NR4A1, PKP2) conflicted with previous reports. Overall, the results demonstrated a limited transcriptional response to PrPSc accumulation, when compared to microglia and macrophage cultures infected with other agents such as viruses and bacteria. This is the first microarray-based analysis of prion accumulation in primary cells derived from a natural TSE-host. Experiment Overall Design: Primary sheep microglial cells were either inoculated with PrPSc (Inoc) or sham-inoculated (Mock) Experiment Overall Design: Three biological replicates per treatment. Experiment Overall Design: Three technical replicates per biological replicate. Experiment Overall Design: biological replicate: Inoc12A, Inoc12B.2, Inoc12C Experiment Overall Design: biological replicate: Mock12A, Mock12B.2, Mock12C Experiment Overall Design: technical replicate - extract: Inoc12A.1, Inoc12A.2, Inoc12A.3 Experiment Overall Design: technical replicate - extract: Inoc12B.2.1, Inoc12B.2.2, Inoc12B.2.3 Experiment Overall Design: technical replicate - extract: Inoc12C.1, Inoc12C.2, Inoc12C.3 Experiment Overall Design: technical replicate - extract: Mock12A.1, Mock12A.2, Mock12A.3 Experiment Overall Design: technical replicate - extract: Mock12B.2.1, Mock12B.2.2, Mock12B.2.3 Experiment Overall Design: technical replicate - extract: Mock12C.1, Mock12C.2, Mock12C.3
2008-11-04 | E-GEOD-12688 | biostudies-arrayexpress
Project description:Comparison of genomic expression profiles in the mesenteric lymph nodes of naturally scrapie infected (clinical and preclinical stages) and control sheep. Expression profiles comparison of 7 clinical and 4 preclinical naturally scrapie infected sheep and 6 controls.
2013-10-29 | E-MTAB-1346 | biostudies-arrayexpress
Project description:Although transmissible spongiform encephalopathies are thought to be mediated by the pathogenic isoform of the prion protein PrPSc, the molecular mechanism underlying neurodegeneration is poorly understood. MicroRNAs (miRNAs) have been shown to cause or influence the pathogenesis of several diseases, however, they were not linked to prion disorders yet. We have addressed the regulation of miRNAs in BSE-infected macaques as a model for human Creutzfeldt-Jacob disease. Applying miRNA microarrays and quantitative RT-PCR, we found that two miRNAs, hsa-miR-342 and hsa-miR-494, are upregulated in the brain of BSE-infected monkeys. Predictions of potential target genes revealed functional links to other neurodegenerative disorders with protein aggregation, including Alzheimer’s and Huntington’s disease. Differential miRNA analysis may be a powerful tool to identify common pathways in the pathogenesis of neurodegeneration.
2009-07-06 | GSE12651 | GEO
Project description:We analyze the transcription of these bovine milk and meat factors (BMMFs) and MS isolates in human HEK293TT cells. While all analyzed DNA agents are readily transcribed, one of the MS brain isolates (MSBI1.176), sharing homology with a transmissible spongiform encephalopathy (TSE)-associated DNA molecule, is transcribed at highest levels. Our results support the transcription of an open reading frame (ORF) encoding a replication-associated protein, which is highly conserved among all isolated BMMFs. In the case of the cow milk isolate CMI1.252, transcription also occurs in a second large ORF. Transcriptome profiling upon BMMF expression identified host cellular gene expression changes related to cell cycle progression and cell viability control, indicating potential pathways for a pathogenic involvement of BMMFs.
2018-02-05 | GSE98192 | GEO
Project description:Comparison of genomic expression profiles in the medulla oblongata of 4 preclinical naturally scrapie infected sheep and 6 controls.. The experiment consisted of the comparison of gene expression profiles in the medulla oblongata of preclinical scrapie and control sheep using oligoDNA CVI-Agilent custom 4x44K chips hybridizations.
2012-11-14 | E-MTAB-866 | biostudies-arrayexpress