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SRP042031
Homo sapiens
4 Downloadable Samples
IlluminaHiSeq2500
Description
Here we explored how the human macrophage response to tumor necrosis factor (TNF) is regulated by human synovial fibroblasts, the representative stromal cell type in the synovial lining of joints that become activated during inflammatory arthritis. Genome-wide transcriptome analysis (RNAseq) showed that co-cultured synovial fibroblasts modulate the expression of approximately one third of TNF-inducible genes in macrophages, including expression of target genes in pathways important for macrophage survival and polarization towards an alternatively activated phenotype. This work furthers our understanding of the interplay between innate immune and stromal cells during an inflammatory response, one that is particularly relevant to inflammatory arthritis. Our findings also identify modulation of macrophage phenotype as a new function for synovial fibroblasts that may prove to be a contributing factor in arthritis pathogenesis. Overall design: Human CD14+ MCSF-differentiated macrophages were cultured with or without synovial fibroblasts in transwell chambers. TNF was added at Day 0, macrophages were harvested at Day 2. Total of 4 samples: (1) macrophages alone (2) macrophages with fibroblasts (3) macrophages with TNF (4) macrophages with fibroblasts and TNF. Macrophage RNA was purified using RNeasy mini kit (Qiagen). Tru-seq sample preparation kits (Illumina) were used to purify poly-A transcripts and generate libraries with multiplexed barcode adaptors. All samples passed quality control on a Bioanalyzer 2100 (Agilent). Paired-end reads (50 x 2 cycles, ~75x106 reads per sample) were obtained on an Illumina HiSeq 2500. The TopHat program was used to align the reads to the UCSC Hg19 human reference genome, while the Cufflinks program allowed for measurements of transcript abundance (represented by Fragments Per Kilobase of exon model per Million mapped reads (FPKM)).
Publication Title
Modulation of TNF-induced macrophage polarization by synovial fibroblasts.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 30 Downloadable Samples
- Illumina HiSeq 2500
Description
Investigated genome-wide changes in gene-expression and chromatin remodeling induced by tumour necrosis factor (TNF) in fibroblast-like synovioctyes (FLS) and macrophages to understand the contribution of FLS to the pathogenesis of rheumatoid arthritis (RA). Overall design: Analysis of transcriptional changes in human RA fibroblast-like synoviocytes (FLS) and macrophages stimulated with or without TNF and I-BET
Publication Title
TNF-induced inflammatory genes escape repression in fibroblast-like synoviocytes: transcriptomic and epigenomic analysis.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 36 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Transcriptomics of distinct subpopulations of synovial fibroblasts from osteoarthritis and rheumatoid arthritis arthroplasty tissues.
Publication Title
Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis.
Sample Metadata Fields
Sex, Age, Disease
View Samples- Mus musculus
- 33 Downloadable Samples
- NextSeq 500, Illumina HiSeq 2000
Description
During chronic stimulation T cells acquire an exhausted phenotype characterized by expression of multiple inhibitory receptors and down-modulation of effector function. While this is required for the protection of the organism from excessive immunopathology, it also prevents successful immunity against persistent viruses or tumor cells. Here we demonstrate that CD8+ T cell exhaustion is characterized by a progressive decline in cellular metabolism. Exhausted T cells exhibit reduced metabolic reserve, impaired fatty acid oxidation and production of mitochondrial reactive oxygen species (ROS). Blockade of inhibitory PD-1/PD-L1 signaling rescued mitochondrial biogenesis, oxidative phosphorylation and ROS production, which was required for efficient restoration of cellular expansion and effector function. Expression of inhibitory receptors and impaired metabolic function was fuled by high amounts of IRF4, BATF and NFAT, which formed a TCR-responsive transcriptional circuit that sustained the transcriptional network responsible for T cell exhaustion. Overall design: Transcriptional profiling of T cells in mice with chronic and acute infections using RNA sequencing
Publication Title
Transcription Factor IRF4 Promotes CD8<sup>+</sup> T Cell Exhaustion and Limits the Development of Memory-like T Cells during Chronic Infection.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Homo sapiens
- 18 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Using array comparative genomic hybridization (aCGH), a large number of deleted genomic regions have been identified in human cancers. However, subsequent efforts to identify target genes selected for inactivation in these regions have often been challenging. We integrated here genome-wide copy number data with gene expression data and non-sense mediated mRNA decay rates in breast cancer cell lines to prioritize gene candidates that are likely to be tumour suppressor genes inactivated by bi-allelic genetic events. The candidates were sequenced to identify potential mutations. This integrated genomic approach led to the identification of RIC8A at 11p15 as a putative candidate target gene for the genomic deletion in the ZR-75-1 breast cancer cell line. We identified a truncating mutation in this cell line, leading to loss of expression and rapid decay of the transcript. We screened 127 breast cancers for RIC8A mutations, but did not find any pathogenic mutations. No promoter hypermethylation in these tumours was detected either. However, analysis of gene expression data from breast tumours identified a small group of aggressive tumours that displayed low levels of RIC8A transcripts. Real-time PCR analysis of 38 breast tumours showed a strong association between low RIC8A expression and the presence of TP53 mutations (P=0.006). We demonstrate a data integration strategy leading to the identification of RIC8A as a gene undergoing a classical double-hit genetic inactivation in a breast cancer cell line, as well as in vivo evidence of loss of RIC8A expression in a subgroup of aggressive TP53 mutant breast cancers.
Publication Title
Data integration from two microarray platforms identifies bi-allelic genetic inactivation of RIC8A in a breast cancer cell line.
Sample Metadata Fields
Sex, Disease, Cell line, Treatment, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
We isolated and selected intestinal adenoma organoids from Apcmin/+; Rosa26LSL-TdTomato; Prox1-CreERT2 mice. After the selection procedure without growth factors, we induced CreERT2 activity and the transcription of tdTomato to label Prox1+ cells by 300 nM 4-hydroxytamoxifen for 16h. tdTomato+ (Prox1+) and tdTomato- cells (enriched for Prox1- cells) were FACS sorted and total RNA was isolated.
Publication Title
Transcription Factor PROX1 Suppresses Notch Pathway Activation via the Nucleosome Remodeling and Deacetylase Complex in Colorectal Cancer Stem-like Cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Gene expression profiling of in vitro differentiated murine Th cell subsets. Flow cytometrically sorted naive Th cells (CD4+ CD44- Foxp3-) were polyclonally stimulated in vitro for 3 days using 4 g/ml plate-bound antibody to CD3 (145-2C11) and 2 g/ml soluble antibody to CD28 (PV-1).
Publication Title
IL-27 and IL-12 oppose pro-inflammatory IL-23 in CD4+ T cells by inducing Blimp1.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The aim of this dataset was to study in detail the transcription kinetics initiated by cytokines IL-12 and IL-4 in early differentiation of Th1 and Th2 cells, respectively.
Publication Title
An integrative computational systems biology approach identifies differentially regulated dynamic transcriptome signatures which drive the initiation of human T helper cell differentiation.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 8 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The distinction between lymphatic and blood vessels is biologically fundamental. Two immortalized cell lines, which have been widely used as models for endothelial cells of blood vascular origin, are the human microvascular endothelial cell line-1 (HMEC-1) and the telomerase-immortalized microvascular endothelial cell line (TIME). However, analysis of protein expression by flow cytometry revealed expression of lymphatic markers on these cell lines. Furthermore, functional in vitro leukocyte transmigration assays demonstrated deficiencies in several steps of the leukocyte extravasation cascade. Hence we performed this microarray analysis of the gene expression in HMEC-1 and TIME. We then compare the expression profiles to those of published blood- and lymphatic endothelial cells.
Publication Title
Plasticity of blood- and lymphatic endothelial cells and marker identification.
Sample Metadata Fields
Cell line
View Samples