Gene expression profile at single cell level of CD8+ T cells and NK cells as part of neonatal antiviral response in C57BL/6J and PrP KO mice infected with mouse cytomegalovirus (MCMV)
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE245338 | GEO | 2024/07/22
REPOSITORIES: GEO
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Project description:Congenital CMV is the leading cause of congenital infections leading to several different neurological complications including ocular pathology. MCMV infeciton of newborn BALB/c mice is a known mouse model to study human infection. Here we evaluated transcriptional changes in the eye caused by blocking CXCR3 during MCMV infection.
2024-11-20 | GSE271252 | GEO
Project description:Congenital CMV is the leading cause of congenital infections leading to several different neurological complications including ocular pathology. MCMV infeciton of newborn BALB/c mice is a known mouse model to study human infection. Here we evaluated transcriptional changes caused by the infection in the eye over the course of development from post natal day 5 to 28.
2024-11-20 | GSE271251 | GEO
Project description:Cytoplasmic RNA granules have emerged as important elements of posttranscriptional and translational regulation. Stress, germinal and neuronal granules contain RNA-binding proteins capable of self-assembly due to prion-like domains. Hyperassembly mediated by these prion-like domains causes several neurodegenerative diseases. Here, we report a subset of the mammalian prion protein (PrP), also prone to self-assembly, propagation and to cause devastating diseases, is a component of naturally occurring messenger ribonucleoproteins (mRNPs) in adult mouse brains. Biomolecules co-purified with PrP revealed a multitude of diverse RNA granule associated proteins and mRNAs encoding members of the translation machinery, indicating a role in a specialized translation process. Importantly, PrP mutations linked to Creutzfeldt-Jakob disease (CJD) or fatal familial insomnia (FFI) severely impaired recovery of mRNPs from preclinical mice, possibly representing a very early pathological process. Thus, mutant PrP may cause dysfunction in RNA regulation, thereby joining the constantly expanding ranks of disease associated RNP granule proteins. The file Enrichment_analysis.xlsx contains mRNAs (FDR < 0.01) co-purified with PrP in both WT sample pools as identified by DESeq2 and the respective gene counts and log2 fold changes for CJD and FFI PrP:IP sample pools.
2015-11-01 | GSE57233 | GEO
Project description:Cytoplasmic RNA granules have emerged as important elements of posttranscriptional and translational regulation. Stress, germinal and neuronal granules contain RNA-binding proteins capable of self-assembly due to prion-like domains. Hyperassembly mediated by these prion-like domains causes several neurodegenerative diseases. Here, we report a subset of the mammalian prion protein (PrP), also prone to self-assembly, propagation and to cause devastating diseases, is a component of naturally occurring messenger ribonucleoproteins (mRNPs) in adult mouse brains. Biomolecules co-purified with PrP revealed a multitude of diverse RNA granule associated proteins and mRNAs encoding members of the translation machinery, indicating a role in a specialized translation process. Importantly, PrP mutations linked to Creutzfeldt-Jakob disease (CJD) or fatal familial insomnia (FFI) severely impaired recovery of mRNPs from preclinical mice, possibly representing a very early pathological process. Thus, mutant PrP may cause dysfunction in RNA regulation, thereby joining the constantly expanding ranks of disease associated RNP granule proteins. The file Enrichment_analysis.xlsx contains mRNAs (FDR < 0.01) co-purified with PrP in both WT sample pools as identified by DESeq2 and the respective gene counts and log2 fold changes for CJD and FFI PrP:IP sample pools. RIP-Seq analysis of mRNAs co-purified with PrP from murine brain cytoplasmic fractions in wild-type (WT), CJD and FFI mice. Each RIP-Seq and control (input) library represents a pool of 12 to 16 co-immunoprecipitation samples out of 3 to 4 mice. To control for post-homogenization artifacts, we conducted an experiment in which we prepared homogenates from WT and PrP-KO (Prnp-/-) mice of different genetic backgrounds (C57BL/6 and 129S4) and identified SNPs in RIP-Seq and control libraries to finally identify specifically co-purified mRNAs.
2015-11-01 | E-GEOD-57233 | biostudies-arrayexpress
Project description:Human cytomegalovirus (HCMV) infection in infants cause severe diseases, such as neonatal hepatitis. However, the single-cell dimensional description of the immune cell alteration during the first virus exposure process in infants, remains poorly understood. The hepatocytes play an essential role in metabolic homeostasis and detoxification. The Concomitant Effects of CMV infection on liver lipid metabolism in infants are still unclear. Here, using single-cell RNA-sequencing, we found MCMV can infect most cell types of infant mice liver, changing the number of immune cells. MCMV infection increases proliferating CD8 effector T cells and a subset of Nos2+ monocytes, which may play important roles in the early anti-viral process. Furthermore, MCMV infection subvert the protein expression profile of lipid metabolism in hepatocytes. Overall, our data provide insights as to how the immune system response to MCMV infection during the early stage of infection, and the impact of infection on lipid metabolism in infant mice hepatocytes.
2023-08-02 | GSE225309 | GEO
Project description:Expression data from NIH-3T3 cells left uninfected or infected with MCMV for 2, 4 or 6h on total RNA as well as newly transcribed RNA labeled for 1-2, 3-4, and 5-6hpi. For newly transcribed RNA, the isolated RNA was labeled for 1h and separated from total cellular RNA following Trizol RNA preparation and thiol-specific biotinylation. We used microarrays to analyze the effects of MCMV infection in total and newly transcribed RNA. During viral infections cellular gene expression is subject to rapid alterations induced by both viral and antiviral mechanisms. In this study, we applied metabolic labeling of newly transcribed RNA with 4-thiouridine (4sU-tagging) to dissect the real-time kinetics of cellular and viral transcriptional activity during lytic murine cytomegalovirus (MCMV) infection. Microarray profiling on newly transcribed RNA obtained from different times during the first six hours of MCMV infection revealed discrete functional networks of cellular genes regulated with distinct kinetics at surprising temporal resolution. Most of these were undetectable in total RNA, either due to low temporal sensitivity of standard gene expression profiling using total RNA, or due to rapid (viral) counter-regulation. Furthermore, metabolic labeling and purification of newly transcribed RNA detailed the real-time kinetics and regulation of viral gene expression in absence of any interfering virion-associated RNA. Both qRT-PCR and next-generation sequencing of newly transcribed RNA demonstrated an unexpected peak of viral gene expression during the first two hours of infection including transcription of immediate early, early and even well characterized late genes. Interestingly, this peak was subject to rapid gene silencing (independent of the multiplicity of infection) with similar transcriptional activity only reached late in infection. For some genes, e.g. m152, this resulted in massive down-regulation of transcriptional activity by 6 hours post infection, which was not even reversed late in infection. Our findings thus highlight the importance of transcriptional activity during the first few hours of CMV infection and hint at novel mechanisms governing the kinetics of viral gene expression. In conclusion, studying real-time transcriptional activity during lytic CMV infection provides intriguing new insights into the regulation of cellular and viral gene expression. NIH-3T3 cells (5th to 15th passage after thawing) were split from confluent plates 24h before start of the experiment. At the beginning of the experiment about 80% confluency was reached. The experiment was started by applying fresh, prewarmed, CO2-equilibrated medium containing either mock or MCMV particles (MOI 1). The MOI was increased by ~10-fold through centrifugal enhancement (2000g, 30min). Labeling was started 1, 3, or 5hpi after the end of centrifugal enhancement.
2013-02-01 | E-GEOD-35919 | biostudies-arrayexpress
Project description:Evidence supporting the role of pathogen exposure in the development of dementia has been mounting for decades. We used murine cytomegalovirus (MCMV) as our model pathogen. We repeated infected mice every 3 months modeling the re-activation/re-infection with MCMV that occurs throughout life. We used Multiome ATAC-seq and RNA-seq to examine changes to the brain of infected animals.
2024-02-01 | GSE220848 | GEO
Project description:A popular method for studying the function of a given protein is to generate and characterize a suitable model deficient for its expression. Most researchers select mouse models for this purpose and investigate proteins of interest in the tissue they are most associated with. For the prion protein (PrP), best known for its role in several invariably fatal neurodegenerative diseases of humans and animals, a natural choice, therefore, would be to undertake such studies with mouse brain samples. We recently documented the surprising observation that PrP deficiency caused a loss or enhancement of NCAM1 polysialylation, dependent on the cell model used. To identify possible causes for this disparity, we set out to systematically investigate the consequence of PrP deficiency on the global proteome in brain tissue and in four distinct cell models. Here we report that PrP deficiency has no discernible impact on the global brain proteome but causes robust but surprisingly divergent changes to the global proteomes of cell models. Our data suggest that careful investigations in cell models, rather than mouse tissue, are the way forward for elucidating the molecular function of PrP.
2016-06-01 | PXD003398 | Pride
Project description:Transcriptome analysis of a population of control animals and RNAi-treated to partially inactivate genes that are homologs to human genes causing Retinitis Pigmentosa. RNA-seq analyses were performed at L3 larval stage in wild type, and smg-1(r861) mutants that have a defective Non-mediated decay pathway. RNA-seq experiments were also performed in adults glp-4(bn2) mutants that lack of germline. synchronized N2 and smg-1(r861) L1 larvae fed for 24 hours at 20 °C with the RNAi clones of prp-6, prp-8, prp-31 and gfp; and 5-day adult glp-4(bn2) worms grown at 25 °C and fed first, for 72 hours with OP50 and next, for 48 more hours with the RNAi clones of prp-8, prp-31 and gfp
2016-07-03 | E-GEOD-72952 | biostudies-arrayexpress
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