This SuperSeries is composed of the SubSeries listed below.
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 SamplesSalp15, a salivary protein of Ixodes ticks, inhibits the activation of naïve CD4 T cells. Treatment with Salp15 results in immunomodulation in different murine models in which these cells participate. The fate of the CD4 T cells activated in the presence of the immunosuppressor or its long-term effects on these cells are however, unknown. We now show that Salp15 binding to CD4 is persistent and induces a long-lasting immunomodulatory effect. The activity of Salp15 results in sustained diminished antibody production against specific and unrelated antigens. Transcriptionally, the salivary protein provokes a sharp acute effect that includes known activation factors, such as Il2, Cd44, or Il2ra, and that fades over time. The long-term effects exerted by Salp15 do not involve the induction of either anergy traits nor increased populations of regulatory T cells. Similarly, the treatment with the immunomodulatory protein does not result in B cell anergy or the generation of myeloid suppressor cells. However, the immunomodulatory protein induces the increased expression of the ectoenzyme, CD73, in regulatory T cells. Our results suggest that the specific regulation of CD73, a known modulator of adenosine levels, by Salp15 results in long-term cross-antigenic immunomodulatory effects. Overall design: Genome-wide changes in gene Expression in mouse CD4 T cells activated with anti-CD3/CD28 in the presence of 25 ug/mL of the tick salivary protein, Salp15 or its inactive control (Salp15deltaP11) were generated by RNAseq.
The immunosuppressive effect of the tick protein, Salp15, is long-lasting and persists in a murine model of hematopoietic transplant.
Age, Specimen part, Cell line, Treatment, Subject, Time
View SamplesThe Her-2/Neu-positive mouse breast cancer cell line was serially co-cultured with minced brain, bone marrow, and lung tissue in an intravital microscopy chamber mounted on the dorsal skinfold of nude mice, alternating with growth in vitro. Gene expression analysis was performed on the cells grown in culture after sorting and further growth in vitro. Gene expression under these growth conditions differed in time and according to the co-cultivated organ tissue. This study reveals genes that are expressed by cells as they adapt differentially to various foreign tissue microenvironments, and may represent a paradigm to discover gene expression changes that occur immediately upon extravasation when cancer metastasizes.
Effects of different tissue microenvironments on gene expression in breast cancer cells.
Cell line
View SamplesWe sought to more precisely characterize the different alpha-synuclein (aSyn) 3’UTR mRNA species in normal and PD human brain. High-throughput, whole-transcriptome sequencing of the 3’UTR ends of polyadenylated mRNA transcripts (termed pA-RNAseq; see Methods) was performed on a cohort of 17 unaffected and 17 PD cerebral cortical tissue samples. This revealed 5 aSyn 3’UTR isoforms, with lengths of 290, 480, 560, 1070 and 2520 nt. Of these, the 560 nt and 2520 nt forms were predominant. The existence and relative preponderance of these species was further confirmed by Northern Blot. We next hypothesized, that aSyn 3’UTR selection might be altered in PD. Comparison of pA-RNAseq profiles from PD and unaffected cerebral cortex samples revealed an increase in the preponderance of the long 3’UTR species (>560 nt) relative to shorter species (<560 nt). Such a relative increase in aSynL was confirmed by Quantitative real-time RT-PCR (rt-qPCR) and appeared specific for PD, as the increase was also observed by comparison to RNA from amyotrophic lateral sclerosis patient samples. We note that the modified aSyn 3’UTR selection associated with PD patient tissue was detected in cerebral cortex tissue, which typically harbors pathological evidence of the disease process without frank cell loss; thus, this phenotype is unlikely to be a secondary consequence of neurodegeneration. Overall design: Comparison of 3''UTR ends of alpha-synuclein in PD and unaffected brain cortex
Alternative α-synuclein transcript usage as a convergent mechanism in Parkinson's disease pathology.
Sex, Specimen part, Disease, Disease stage, Subject
View SamplesComparison of gene expression signatures in hESC-derived gastrointestinal precursors, enterospheres and primary human tissues to determine lineage and cell type identity.
Functional Enterospheres Derived In Vitro from Human Pluripotent Stem Cells.
Specimen part, Cell line
View SamplesBased on preliminary data demonstrating that macrophages are critical regulators of Helicobacter pylori colonization and gastric pathology in mice, we sought to investigate how macrophages may serve as bacterial reservoirs of intracellular H. pylori. Overall design: BMDM were isolated from WT and PPARg-/- mice and cultured with M-CSF for 7 days to promote macrophage differentiation. Fully differentiation macrophages were challenged with H. pylori strains SS1 at an MOI of 10 for 15 minutes. Extracellular bacteria was then eliminated by gentamycin treatment. Cells were collected at 0, 60, 120, 240, 360 and 720 minutes post gentamycin treatment to ascertain whole transcriptome differential gene expression during infection.
Identification of new regulatory genes through expression pattern analysis of a global RNA-seq dataset from a Helicobacter pylori co-culture system.
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View SamplesTo analyze the gene expression alteration after stroke, we used Middle Cerebral Artery Occlusion model of rats. By comparing with Sham operated rats, we extracted the mRNAs whose expressions are alterated by stroke.
Gene Expression Analysis of the Effect of Ischemic Infarction in Whole Blood.
Sex, Age, Specimen part
View SamplesReactivation of latent HCMV is a significant infectious complication of organ transplantation, and current therapies target viral replication once reactivation of transcriptionally silent, latent virus has already occurred. The specific molecular pathways that activate viral gene expression are not well understood. Our studies aim to identify these factors, with the goal of developing novel therapies that prevent transcriptional reactivation in transplant recipients. MCMV is a valuable model for studying latency and reactivation of CMV induced by organ transplantation. We previously demonstrated that transplantation of MCMV-latently infected kidneys into allogeneic recipients induces transcriptional reactivation of immediate early (IE) gene expression within 48 hr.
Transplant-induced reactivation of murine cytomegalovirus immediate early gene expression is associated with recruitment of NF-κB and AP-1 to the major immediate early promoter.
Age, Specimen part
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