Aim: To examine transcriptional changes in DLD-1 cells exposed to softer matrices (2 kPa and 55 kPa) and identify the chromosomes that are enriched with maximmally deregulated genes Methods: DLD-1 cells (otherwise growing on stiff tissue culture plastic substrates) were exposed to softer matrices for 90 minutes and to collagen coated glass coverslips (served as control) served as control) Results: RNA sequencing revealed nearly equivalent transcriptional deregulation in cells on both the polyacrylamide matrices (783 genes up and 872 genes down on 2 kPa, 649 genes up and 783 genes down on 55 kPa) when compared to cells on glass. Additionally, GO classification revealed that unique sets of transcriptionally deregulated genes (log fold=2) belonged to pathways associated with transcription regulation, chromatin organization, cell cycle and DNA damage/repair Results: We identified chromosomes 1, 2, 3, 6, 7, 10, 12, 14, 17 and 19 to be maximally enriched with the deregulated genes on softer matrices (log fold=2), while chromosomes 13, 18 and 21 showed minimal enrichment of deregulated genes. We also examined the spatial organization of chromosome 1, 18 and 19 territories in cells on softer matrices (using 3D-FISH) and observed that these chromosomes were mislocalized away from their conserved nuclear locations Conclusions: Our study reports the transcriptomic changes in DLD-1 cells upon lowering of extracellular substrate stiffnes and its impact on the spatial positioning of chromosome territories Overall design: RNA Seq profiles for DLD-1 cells on soft polyacrylamide matrices of ~2 kPa and ~55 kPa (reference - glass) were generated across 2 independent biological replicates using Illumina HiSeq platform
Emerin modulates spatial organization of chromosome territories in cells on softer matrices.
Cell line, Subject
View SamplesImmune cell infiltration in myositis were by examining microarray expression profiles in muscle biopsies from 31 myositis patients and 5 normal controls.
Genomic signatures characterize leukocyte infiltration in myositis muscles.
Sex, Specimen part, Disease, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The plasma cell signature in autoimmune disease.
Specimen part, Treatment, Time
View SamplesObjective: Production of pathogenic autoantibodies by self-reactive plasma cells (PC) is a hallmark of autoimmune diseases. Investigating the prevalence of PC in autoimmune disease and their relationship with known pathogenic pathways may increase our understanding of the role of PC in disease progression and treatment response. Methods: We developed a sensitive gene expression based method to overcome the challenges of measuring PC using flow cytometry. Whole genome microarray analysis of sorted cellular fractions identified a panel of genes, IGHA, IGJ, IGKC, IGKV, and TNFRSF17, expressed predominantly in PC. The sensitivity of the PC signature score created from the combined expression levels of these genes was assessed through ex vivo experiments with sorted cells. This PC gene expression signature was used for monitoring changes in PC levels following anti-CD19 therapy; evaluating the relationship between PC and other autoimmune disease-related genes; and estimating PC levels in affected blood and tissue from multiple autoimmune diseases. Results: The PC signature was highly sensitive and capable of detecting as few as 300 PCs. The PC signature was reduced over 90% in scleroderma patients following anti-CD19 treatment and this reduction was highly correlated (r = 0.77) with inhibition of collagen gene expression. Evaluation of multiple autoimmune diseases revealed 30-35% of lupus, rheumatoid arthritis, and scleroderma patients with increased PC levels. Conclusion: This newly developed PC signature provides a robust and accurate method to measure PC levels in the clinic. Our results highlight subsets of patients across multiple autoimmune diseases that may benefit from PC depleting therapy.
The plasma cell signature in autoimmune disease.
Specimen part, Treatment, Time
View SamplesObjective: Production of pathogenic autoantibodies by self-reactive plasma cells (PC) is a hallmark of autoimmune diseases. Investigating the prevalence of PC in autoimmune disease and their relationship with known pathogenic pathways may increase our understanding of the role of PC in disease progression and treatment response. Methods: We developed a sensitive gene expression based method to overcome the challenges of measuring PC using flow cytometry. Whole genome microarray analysis of sorted cellular fractions identified a panel of genes, IGHA, IGJ, IGKC, IGKV, and TNFRSF17, expressed predominantly in PC. The sensitivity of the PC signature score created from the combined expression levels of these genes was assessed through ex vivo experiments with sorted cells. This PC gene expression signature was used for monitoring changes in PC levels following anti-CD19 therapy; evaluating the relationship between PC and other autoimmune disease-related genes; and estimating PC levels in affected blood and tissue from multiple autoimmune diseases. Results: The PC signature was highly sensitive and capable of detecting as few as 300 PCs. The PC signature was reduced over 90% in scleroderma patients following anti-CD19 treatment and this reduction was highly correlated (r = 0.77) with inhibition of collagen gene expression. Evaluation of multiple autoimmune diseases revealed 30-35% of lupus, rheumatoid arthritis, and scleroderma patients with increased PC levels. Conclusion: This newly developed PC signature provides a robust and accurate method to measure PC levels in the clinic. Our results highlight subsets of patients across multiple autoimmune diseases that may benefit from PC depleting therapy.
The plasma cell signature in autoimmune disease.
Specimen part
View SamplesThe goal of this experiment is to characterize the ability of IRAK4 kinase inhibitors to block TLR7 or TLR9 induced gene transcription in human PBMCs. PBMCs from two donors were pretreated with compound for 30 minutes and stimulated with gardiquimod (TLR7 ligand) or ODN 2216 (TLR9 ligand) for 5 hrs. Compound treated gene expression profiles wil be compared to untreated.
Selective IRAK4 Inhibition Attenuates Disease in Murine Lupus Models and Demonstrates Steroid Sparing Activity.
Specimen part, Subject
View SamplesCD14+ monocytes sorted from the synovial fluid or peripheral blood of rheumatoid arthritis patients were analyzed by full transcriptome microarray analysis. Monocytes from healthy control samples (peripheral blood) were also profiled.
MicroRNA-155 contributes to enhanced resistance to apoptosis in monocytes from patients with rheumatoid arthritis.
Specimen part, Disease, Disease stage, Subject
View SamplesCotton fiber were used for the expression analysis at different developmental stages
Transcriptome dynamics during fibre development in contrasting genotypes of Gossypium hirsutum L.
No sample metadata fields
View SamplesAnalysis of step-wise transcriptome changes of reprogrammed cells in different stages during induced reprogramming.
Genome-wide functional analysis reveals factors needed at the transition steps of induced reprogramming.
No sample metadata fields
View SamplesPurpose: The goal of this study is to identify differentially expressed genes in pry-1/Axin mutant compare to N2 wild-type (WT). Our study represents the first analysis of Axin transcriptome in C. elegans and facilitates investigations of axin mediated processes. Overall design: Whole animal total RNA was extracted from L1 synchronized worms and mRNA profiles of WT and pry-1(mu38) animals were generated by paired end deep sequencing, using Illumina HISeq 2000. The sequence reads that passed quality filters were analyzed using ce6 with Burrows–Wheeler Aligner (BWA) followed by eXpress to estimate transcript abundances. Differentially-expressed genes were called at a false discovery rate (FDR) of 0.05% using the DESeq package in R.
PRY-1/Axin signaling regulates lipid metabolism in Caenorhabditis elegans.
Cell line, Subject
View Samples