Cross-species comparative gene expression profiling was performed to identify differentially expressed genes conserved in aggressive B lymphomas.
Identification of candidate B-lymphoma genes by cross-species gene expression profiling.
Sex, Specimen part
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Common genetic variants modulate pathogen-sensing responses in human dendritic cells.
Sex, Age, Race, Subject
View SamplesVariation in individuals' responses to environmental factors is believed to influence susceptibility to complex diseases in humans. The genetic basis of such variation is poorly understood. We measured gene expression from resting and stimulated dendritic cells (DCs) derived from the peripheral blood of healthy individuals. We stimulated the primary DCs with E. coli lipopolysaccharide (LPS) or influenza virus. Using serial replicate samples, we selected genes that showed evidence of reproducibility within the serial replicates.
Common genetic variants modulate pathogen-sensing responses in human dendritic cells.
Sex, Age, Race, Subject
View SamplesThe identification of lymphocyte subsets with non-overlapping effector functions has been pivotal to the development of targeted therapies in immune mediated inflammatory diseases (IMIDs). Yet, despite their key role in disease, it remains unclear whether fibroblast subclasses with non-overlapping functions also exist and are responsible for the wide variety of tissue driven pathologies observed in IMIDs such as inflammation and damage . Here we identify and describe the biology of distinct subsets of fibroblasts responsible for mediating either inflammation or tissue damage in arthritis. We show that deletion of FAPa+ synovial cells suppressed both inflammation and bone erosions in murine models of resolving and persistent arthritis. Single cell transcriptional analysis identified two distinct fibroblast subsets: FAPa+ THY1+ immune effector fibroblasts located in the synovial sub-lining, and FAPa+ THY1- destructive fibroblasts restricted to the synovial lining. When adoptively transferred into the joint, FAPa+ THY1- fibroblasts selectively mediate bone and cartilage damage with little effect on inflammation whereas transfer of FAPa+ THY1+ fibroblasts resulted in a more severe and persistent inflammatory arthritis, with minimal effect on bone and cartilage. Our findings describing anatomically discrete, functionally distinct fibroblast subsets with non-overlapping functions have important implications for cell based therapies aimed at modulating inflammation and tissue damage. Overall design: Serum transfer inflammatory arthritis (STIA) was induced by intravenous injection of 100 µl of arthritogenic KRN serum into naive C57BL/6 mice. From these mice, CD45-ve live Podoplanin (PDPN)+ synovial cells from hind limb joints were sort purified at day 9 (n=3 biological replicates, each comprised of cells from the joints of three animals). Individuals subsets of CD45- PDPN+ cells were further sort puified in the following populations FAP?+ THY1- (n=10 mice); FAP?+ THY+ (n=13 mice); FAP?- THY1+ (n=7 mice) and FAP?- THY1- (n=5 mice). Small bulk RNA sequencing was performed on each of these cell populations with each sample representing a biological replicate comprising of cells isolated from the synovial joints of both hind limbs from a single mouse).
Distinct fibroblast subsets drive inflammation and damage in arthritis.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis.
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesTranscriptomics of distinct subpopulations of synovial fibroblasts from osteoarthritis and rheumatoid arthritis arthroplasty tissues.
Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis.
Sex, Age, Disease
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes.
Sex, Age, Specimen part
View SamplesGene expression profiling of CD4 T-Cells (CD4+CD62L+) from human peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from healthy individuals from the Boston area.
Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes.
Sex, Age, Specimen part
View SamplesGene expression profiling of Monocytes (CD14+CD16-) from human peripheral blood mononuclear cells (PBMCs). PBMCs were isolated from healthy individuals from the Boston area.
Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes.
Sex, Specimen part
View SamplesOne of our new major finding among the genes that contributes to MS susceptibility is ICSBP1. The so called disease modifying therapies like interferon-beta (IFN-), possibly acting on the peripheral T-cells, reduce the disease activity and the clinical progression, with a MRI-detectable effect in preventing lesion burden and cerebral atrophy development in RR-MS. It suggests a critical role of peripheral blood mononuclear cells (PBMCs) immune response and modulation in developing inflammation in the brain. We tested the hypothesis that the genetic effect of the susceptible allele ICSBP1 can impact the gene expression profile of molecules belonging to the interferon pathway. We therefore interrogated the PBMC for changes in gene expression profile. We correlate those changes with the minor allele frequency for ICSBP1, performing independent quantitative trait analysis for each treatment category. Expression Quantitative Trait Loci Association with a p value < 0.05 have been used in follow up analysis. The regression coefficient of the Quantitative trait association represents the degree of correlation between the gene expression for each interrogated target gene and the minor allele frequency of the SNP for our gene of interest. This coefficient has been used as input in the subsequent Gene Set Enrichment Analysis performed in a pre-ranked approach. The resulting GSEA-SNP method rests on the assumption that SNPs underlying a disease phenotype might affect genes constituting a signaling pathway or genes with a common regulation. Therefore, GSEA-SNP can facilitate the identification of pathways or of underlying biological mechanisms.
Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci.
Specimen part
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