MHC-I overexpression in muscle biopsies is a hallmark of inflammatory myopathies.However the mechanisms of MHC-I overexpression in each disease is not well understood. Microarray analysis from MHC-I-microdissected myofibers showed a differential expression signature in each inflammatory myopathy. Innate immunity and IFN-I pathways are upregulated vs healthy controls, specifically in dermatomyositis (DM).
Altered RIG-I/DDX58-mediated innate immunity in dermatomyositis.
Specimen part, Disease
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Survival transcriptome in the coenzyme Q10 deficiency syndrome is acquired by epigenetic modifications: a modelling study for human coenzyme Q10 deficiencies.
Sex, Age, Specimen part, Treatment, Subject
View SamplesCoenzyme Q10 deficiency syndrome includes a clinically heterogeneous group of mitochondrial diseases characterized by low content of CoQ10 in tissues. The only currently available treatment is supplementation with CoQ10, which improves the clinical phenotype in some patients but does not reverse established damage. We analyzed the transcriptome profiles of fibroblasts from different patients irrespective of the genetic origin of the disease. These cells showed a survival genetic profile apt at maintaining growth and undifferentiated phenotype, promoting anti-apoptotic pathways, and favoring bioenergetics supported by glycolysis and low lipid metabolism. WE conclude that the mitochondrial dysfunction caused byCoQ10 deficiency induces a stable survival adaptation of somatic cells from patients.
Survival transcriptome in the coenzyme Q10 deficiency syndrome is acquired by epigenetic modifications: a modelling study for human coenzyme Q10 deficiencies.
Sex, Specimen part, Treatment
View SamplesCoenzyme Q10 deficiency syndrome includes a clinically heterogeneous group of mitochondrial diseases characterized by low content of CoQ10 in tissues. The only currently available treatment is supplementation with CoQ10, which improves the clinical phenotype in some patients but does not reverse established damage.
Survival transcriptome in the coenzyme Q10 deficiency syndrome is acquired by epigenetic modifications: a modelling study for human coenzyme Q10 deficiencies.
Sex, Age, Treatment, Subject
View SamplesWe are investigating the transcriptional response of newborns in response to prenatal arsenic exposure
Activation of inflammation/NF-kappaB signaling in infants born to arsenic-exposed mothers.
No sample metadata fields
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A multi-omic analysis reveals the regulatory role of CD180 during the response of macrophages to Borrelia burgdorferi.
Age, Specimen part, Treatment
View SamplesMacrophages are cells of the innate immune system with the ability to phagocytose and induce a global pattern of responses that depend on several signalling pathways. We have determined the biosignature of murine bone marrow-derived macrophages and human blood monocytes using transcriptomics and proteomics approaches. We identified a common pattern of genes transcriptionally regulated that overall indicate that the response to B. burgdorferi involves the interaction of spirochetal antigens with several inflammatory pathways corresponding to primary (triggered by pattern recognition receptors) and secondary (induced by proinflammatory cytokines) responses. We also show that the Toll-like receptor family member, CD180 is downregulated by the stimulation of macrophages, but not monocytes, with the spirochete. Silencing Cd180 results in increased phagocytosis while tempering the production of the proinflammatory cytokine, TNF. Cd180-silenced cells produced increased levels of Itgam and surface CD11b, suggesting that the regulation of CD180 by the spirochete initiates a cascade that increases the CR3-mediated phagocytosis of the bacterium while repressing the consequent inflammatory response.
A multi-omic analysis reveals the regulatory role of CD180 during the response of macrophages to Borrelia burgdorferi.
Specimen part, Treatment
View SamplesMacrophages are cells of the innate immune system with the ability to phagocytose and induce a global pattern of responses that depend on several signalling pathways. We have determined the biosignature of murine bone marrow-derived macrophages and human blood monocytes using transcriptomics and proteomics approaches. We identified a common pattern of genes transcriptionally regulated that overall indicate that the response to B. burgdorferi involves the interaction of spirochetal antigens with several inflammatory pathways corresponding to primary (triggered by pattern recognition receptors) and secondary (induced by proinflammatory cytokines) responses. We also show that the Toll-like receptor family member, CD180 is downregulated by the stimulation of macrophages, but not monocytes, with the spirochete. Silencing Cd180 results in increased phagocytosis while tempering the production of the proinflammatory cytokine, TNF. Cd180-silenced cells produced increased levels of Itgam and surface CD11b, suggesting that the regulation of CD180 by the spirochete initiates a cascade that increases the CR3-mediated phagocytosis of the bacterium while repressing the consequent inflammatory response. Overall design: Genome-wide changes in gene Expression in mouse bone marrow-derived macrophages stimulated with Borrelia burgdorferi or left unstimulated were generated by RNAseq.
Regulation of macrophage activity by surface receptors contained within Borrelia burgdorferi-enriched phagosomal fractions.
Age, Specimen part, Cell line, Treatment, Subject
View SamplesWe analyzed the changes in the spinal cord transcriptome after a spinal cord contusion injury and MSC or OEC transplantation. The cells were injected immediately or 7 days after the injury. The mRNA of the spinal cord injured segment was extracted and analyzed by microarray at 2 and 7 days after cell grafting.
Gene expression changes in the injured spinal cord following transplantation of mesenchymal stem cells or olfactory ensheathing cells.
Treatment
View SamplesNAD(P)H:quinone Oxidoreductase (NQO1) is essential for cell defense against reactive oxidative species, cancer, and metabolic stress. Recently, NQO1 was found in ribonucleoprotein (RNP) complexes, but NQO1-interacting mRNAs and the functional impact of such interactions are not known. Here, we used ribonucleoprotein immunoprecipitation (RIP) and microarray analysis to identify comprehensively the subset of NQO1 target mRNAs in human hepatoma HepG2 cells. One of its main targets, SERPINA1 mRNA, encodes the serine protease inhibitor -1-antitrypsin, A1AT, which is associated with disorders including obesity-related metabolic inflammation, chronic obstructive pulmonary disease (COPD), liver cirrhosis and hepatocellular carcinoma. Biotin pulldown analysis indicated that NQO1 can bind the 3 untranslated region (UTR) and the coding region (CR) of SERPINA1 mRNA. NQO1 did not affect SERPINA1 mRNA levels; instead, it enhanced the translation of SERPINA1 mRNA, as NQO1 silencing decreased the size of polysomes forming on SERPINA1 mRNA and lowered the abundance of A1AT. Luciferase reporter analysis further indicated that NQO1 regulates SERPINA1 mRNA translation through the SERPINA1 3UTR. Accordingly, NQO1-KO mice had reduced hepatic and serum levels of A1AT and increased activity of neutrophil elastase, one of the main targets of A1AT. We propose that this novel mechanism of action of NQO1 as RNA-binding protein may help to explain its pleiotropic biological effects.
Novel RNA-binding activity of NQO1 promotes SERPINA1 mRNA translation.
Specimen part, Cell line, Treatment
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