RNA-seq of CH12F3 and Lig4-/- CH12F3 cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE154443 | GEO | 2020/07/15
REPOSITORIES: GEO
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Project description:RNA-seq of CH12F3 and Lig4-/- CH12F3 cells
| PRJNA646268 | ENA
Project description:Macrophages play fundamental roles in regulation of inflammatory responses to pathogens, resolution of inflammation and tissue repair, and maintenance of tissue homeostasis. The long (L) and short (S) isoforms of SP-R210/MYO18A, a macrophage receptor for surfactant protein A (SP-A) and C1q, regulate basal and inflammatory macrophage phenotype at multiple gene expression, translational, and subcellular levels in addition to their SP-A and C1q-mediated functions; disruption of L renders macrophages hyper-inflammatory, although the underlying mechanism had previously been unexplored. We questioned whether disruption of the L isoform would alter the global genomic responses. RNA sequencing analysis of SP-R210L(DN) macrophages revealed basal and influenza induced upregulation of genes associated with inflammatory pathways, including TLR, RIG-I, NOD, and cytoplasmic DNA signaling, whereas knockdown of both SP-R210 isoforms (L and S) only resulted in increased RIG-I and NOD signaling. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis showed increased genome-wide deposition of the pioneer transcription factor PU.1 in SP-R210L(DN) compared to WT cells. ChIP-seq analysis of histone H3 methylation showed alterations in both repressive (H3K9me3 and H3K27me3) and transcriptionally active (H3K9me3) histone marks. Influenza A virus (IAV) infection, which stimulates an array of cytosolic and TLR-mediated antiviral mechanisms, resulted in differential redistribution between proximal promoter and distal sites and decoupling of PU.1 binding from Toll-like receptor regulated gene promoters in SP-R210L(DN) cells. Our findings suggest that SP-R210L-deficient macrophages are poised with an open PU.1-primed chromatin conformation to rapidly respond to inflammatory and metabolic stimuli.
2020-12-31 | GSE164035 | GEO
Project description:Macrophages play fundamental roles in regulation of inflammatory responses to pathogens, resolution of inflammation and tissue repair, and maintenance of tissue homeostasis. The long (L) and short (S) isoforms of SP-R210/MYO18A, a macrophage receptor for surfactant protein A (SP-A) and C1q, regulate basal and inflammatory macrophage phenotype at multiple gene expression, translational, and subcellular levels in addition to their SP-A and C1q-mediated functions; disruption of L renders macrophages hyper-inflammatory, although the underlying mechanism had previously been unexplored. We questioned whether disruption of the L isoform would alter the global genomic responses. RNA sequencing analysis of SP-R210L(DN) macrophages revealed basal and influenza induced upregulation of genes associated with inflammatory pathways, including TLR, RIG-I, NOD, and cytoplasmic DNA signaling, whereas knockdown of both SP-R210 isoforms (L and S) only resulted in increased RIG-I and NOD signaling. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis showed increased genome-wide deposition of the pioneer transcription factor PU.1 in SP-R210L(DN) compared to WT cells. ChIP-seq analysis of histone H3 methylation showed alterations in both repressive (H3K9me3 and H3K27me3) and transcriptionally active (H3K9me3) histone marks. Influenza A virus (IAV) infection, which stimulates an array of cytosolic and TLR-mediated antiviral mechanisms, resulted in differential redistribution between proximal promoter and distal sites and decoupling of PU.1 binding from Toll-like receptor regulated gene promoters in SP-R210L(DN) cells. Our findings suggest that SP-R210L-deficient macrophages are poised with an open PU.1-primed chromatin conformation to rapidly respond to inflammatory and metabolic stimuli.
2020-12-31 | GSE164034 | GEO
Project description:The goal of this study is to explore molecular mechanisms underpinning the progression-associated host-microbial interactions in IPF. Multi-omics analysis revealed that the majority (8/11) of the progression-associated pathways were involved in inflammatory response and pattern recognition receptors (PRRs), including NOD-, TOLL- and RIG-I-like receptor pathways. Microbial community richness was correlated with all of the three PRRs (Pearson's p<0.007). The known IPF-progression marker Streptococcus (OTU1345) was correlated with NOD like receptor signaling pathway (p=0.047). Up-regulated genes in PBMCs of CpG-ODN responsive patients were over-represented in 22 canonical pathways (FDR<0.01). Network modeling revealed that 14/22 pathways were significantly correlated with community diversity (Shannon's index) and three genera (Otu1341 Prevotella, OTU1348 Staphylococcus, and OTU1302 Pseuodomonadacea), as well as 10/11 host gene co-expression modules. Toll-like receptor signaling pathway was mutually linked by CpG-response, Otu1341 and microbial Shannon's index. Notably, OTU1341 and IPF-progression marker OTU1348 were also correlated with TLR9 (r=0.48, p=3x10-5; r=0.38, p=0.002, respectively). These findings suggest that PRR and immune response signaling pathways play a central role in PFS-associated host-microbial interactions and the probifbrotic differentiation induced by CpG-ODN upon TLR9 stimulation.
2016-09-15 | GSE85268 | GEO
Project description:The RIG-I like receptors (RLRs) RIG-I and MDA5 are cytosolic RNA helicases best characterized as restriction factors for RNA viruses. However, evidence suggests RLRs participate in innate immune recognition of other pathogens, including DNA viruses. Kaposi's sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus and the etiological agent of Kaposi's sarcoma and primary effusion lymphoma (PEL). We demonstrate that RIG-I and MDA5 restrict KSHV lytic reactivation in PEL. By performing fRIP-Seq, we define the in vivo RLR substrates and demonstrate that RIG-I and MDA5-mediated restriction is facilitated exclusively by the recognition of host-derived RNAs.
2018-10-11 | GSE116650 | GEO
Project description:Rainbow trout (Oncorhynchus mykiss), an economically important cold-water fish cultured worldwide, suffers from infectious hematopoietic necrosis virus (IHNV) infection, resulting in huge financial losses. In order to understand the immune response of rainbow trout during virus infection, we explored trout skin transcriptome profiles following IHNV challenge, and identified 6905 differentially expressed genes (DEGs). Transcriptome analysis revealed numerous DEGs involved in immune responses, such as NOD1, NLRC3, NLRC5, TLR3, TLR7/8, TRIM25, DHX58, IFIH1, IRF3/7, STAT1, TRAF3, MX1 and HSP90A1. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that DEGs were significantly enriched in various immune-related terms including immune system process, innate immune response and regulation of immune effector process and pathways of cytokine-cytokine receptor interactions, NOD-like receptor signaling, RIG-I-like receptor signaling, Toll-like receptor signaling, JAK-STAT signaling, Chemokine signaling pathway, and TNF signaling pathway. In addition, protein-protein interaction network (PPI) was used to display highly interactive DEG networks involving immune-related pathways. The expression trends of 16 DEGs were further verified by quantitative real-time PCR, which confirmed the reliability of the transcriptome sequencing results. This study expands our understanding of the immune response of rainbow trout infected with IHNV, and provides valuable resources for future studies on the immune molecular mechanism and disease resistance breeding.
2022-12-28 | GSE221722 | GEO
Project description:The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic RIG-I and viral RNA structures that contain short hairpin dsRNA and 5M-bM-^@M-^Y triphosphate (5M-bM-^@M-^Yppp) terminal structure. In the present study, an RNA agonist of RIG-I was synthesized in vitro and shown to stimulate RIG-I-dependent antiviral responses at concentrations in the picomolar range. In human lung epithelial A549 cells, 5M-bM-^@M-^YpppRNA specifically stimulated multiple parameters of the innate antiviral response, including IRF3, IRF7 and STAT1 activation, andinduction of inflammatory and interferon stimulated genes - hallmarks of a fully functional antiviral response. Evaluation of the magnitude and duration of gene expression by transcriptional profiling identified a robust, sustained and diversified antiviral and inflammatory response characterized by enhanced pathogen recognition and interferon (IFN)signaling. Bioinformatics analysis further identified a transcriptional signature uniquely induced by 5M-bM-^@M-^YpppRNA, and not by IFNM-NM-1-2bthat included a constellation of IRF7 and NF-kB target genes capable of mobilizing multiple arms of the innate and adaptive immune response. Treatment of primary PBMCs or lung epithelial A549 cells with 5M-bM-^@M-^YpppRNA provided significant protection against a spectrum of RNA and DNA viruses. In C57Bl/6 mice, intravenous administration of 5M-bM-^@M-^YpppRNA protected animals from a lethal challenge with H1N1 Influenza, reduced virus titers in mouse lungs and protected animals from virus-induced pneumonia. Strikingly, the RIG-I-specific transcriptional response afforded partial protection from influenza challenge, even in the absence of type I interferon signaling. This systems approach providestranscriptional, biochemical, and in vivo analysis of the antiviral efficacy of 5M-bM-^@M-^YpppRNA and highlights the therapeutic potential associated with the use of RIG-I agonists as broad spectrum antiviral agents. Kinetic analysis of A549 cells treated with 5'pppRNA and analyzed at 1h, 2h, 4h, 6h, 8h, 12h, 24h or 48h.
2014-08-21 | E-GEOD-60573 | biostudies-arrayexpress
Project description:The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic RIG-I and viral RNA structures that contain short hairpin dsRNA and 5M-bM-^@M-^Y triphosphate (5M-bM-^@M-^Yppp) terminal structure. In the present study, an RNA agonist of RIG-I was synthesized in vitro and shown to stimulate RIG-I-dependent antiviral responses at concentrations in the picomolar range. In human lung epithelial A549 cells, 5M-bM-^@M-^YpppRNA specifically stimulated multiple parameters of the innate antiviral response, including IRF3, IRF7 and STAT1 activation, andinduction of inflammatory and interferon stimulated genes - hallmarks of a fully functional antiviral response. Evaluation of the magnitude and duration of gene expression by transcriptional profiling identified a robust, sustained and diversified antiviral and inflammatory response characterized by enhanced pathogen recognition and interferon (IFN)signaling. Bioinformatics analysis further identified a transcriptional signature uniquely induced by 5M-bM-^@M-^YpppRNA, and not by IFNM-NM-1-2bthat included a constellation of IRF7 and NF-kB target genes capable of mobilizing multiple arms of the innate and adaptive immune response. Treatment of primary PBMCs or lung epithelial A549 cells with 5M-bM-^@M-^YpppRNA provided significant protection against a spectrum of RNA and DNA viruses. In C57Bl/6 mice, intravenous administration of 5M-bM-^@M-^YpppRNA protected animals from a lethal challenge with H1N1 Influenza, reduced virus titers in mouse lungs and protected animals from virus-induced pneumonia. Strikingly, the RIG-I-specific transcriptional response afforded partial protection from influenza challenge, even in the absence of type I interferon signaling. This systems approach providestranscriptional, biochemical, and in vivo analysis of the antiviral efficacy of 5M-bM-^@M-^YpppRNA and highlights the therapeutic potential associated with the use of RIG-I agonists as broad spectrum antiviral agents. A549 cells were either non-treated, treated with RNAiMax only, transfected with 5'pppRNA, or treated with IFNa-2b and analysed at 6h or 24h.
2014-08-21 | E-GEOD-60572 | biostudies-arrayexpress
Project description:VSV-M2 is recognized by cytosolic RIG-I. Notably, 5'-triphosphate RNA molecules derived from either viral RNA or from the synthetically produced 3pRNA can also induce RIG-I activation. MDA5 stimulation is achieved using complexed poly(I:C), a synthetic analog of viral dsRNA. To test whether the RIG-I and MDA5 ligands 3pRNA and poly(I:C) can be used in their complexed structures to decipher RNA virus-induced sickness behavior in vivo, we first compared the tissue-specific signaling pathways after systemic challenge with VSV-M2 and the RIG-I and MDA5 ligands, respectively. A whole-genome expression analysis using splenic cells was carried out using an Affymetrix Mouse Gene 2.1 ST Array.
2016-04-20 | GSE74015 | GEO
Project description:The goals of this study are to evaluate the gene expression of PBMC in stroke patients with atherosclerosis compared with healthy donors. PBMC mRNA profiles of stroke patients and healthy donors were generated by sequencing using Illumina. We detected 60613 transcripts, and there are there are 470 significant genes expression upregulated (fold change > 2 and p value < 0.05) and 355 downregulated (fold change < 0.5 and p value < 0.05) in atherosclerotic patients versus healthy individuals. We found that differentially expressed genes were significantly enriched among immune response and virus defense categories by functional KEGG analysis, including TNF signaling pathway, Toll-like receptor signaling pathway, NF-kappa B signaling pathway, NOD-like receptor signaling pathway, RIG-like receptor signaling pathway and apoptosis.
2023-03-01 | GSE199819 | GEO