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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
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
We did transcriptome profiling for monocytes treated with or without IFNg to characterize IFNg response. Overall design: Human primary monocytes were cultured for 24 hours with or without IFNg, harversted and prepared for RNA for RNAseq.
Publication Title
IFN-γ Induces Histone 3 Lysine 27 Trimethylation in a Small Subset of Promoters to Stably Silence Gene Expression in Human Macrophages.
Sample Metadata Fields
Specimen part, Subject
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
- 132 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
DNA repair is an essential cellular process required to maintain genomic stability. Every cell is subjected to thousands of DNA lesions daily under normal changes in transcription. Transcription is a primary process where protein amount and function can be regulated. One aspect of the transcriptional IR response that little is known about on a whole genome basis is alternative transcription. These investigations focus on the response to IR at the exon level in human cells but also at the whole gene level. Whole genome exon arrays were utilized to comprehensively characterize radiation-induced transcriptional expression products in two human cell types, namely EBV-transformed lymphoblast and primary fibroblast cell lines.
Publication Title
DNA repair genes: alternative transcription and gene expression at the exon level in response to the DNA damaging agent, ionizing radiation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaHiSeq2000
Description
IFN-g primes macrophages for enhanced inflammatory activation by TLRs and microbial killing, but little is known about the regulation of cell metabolism or mRNA translation during priming. We found that IFN-g regulates macrophage metabolism and translation in an integrated manner by targeting mTORC1 and MNK pathways that converge on the selective regulator of translation initiation eIF4E. Physiological downregulation of the central metabolic regulator mTORC1 by IFN-g was associated with autophagy and translational suppression of repressors of inflammation such as HES1. Genome-wide ribosome profiling in TLR2-stimulated macrophages revealed that IFN-g selectively modulates the macrophage translatome to promote inflammation, further reprogram metabolic pathways, and modulate protein synthesis. These results add IFN-g-mediated metabolic reprogramming and translational regulation as key components of classical inflammatory macrophage activation. Overall design: RPF and RNAseq libraries were generated from mock or IFN-g-primed human macrophages. Cells were stimulated with Pam3Cys and harvested at 4 hours. Libraries were generated using protocol modified from Illumina Truseq technology.
Publication Title
Interferon-γ regulates cellular metabolism and mRNA translation to potentiate macrophage activation.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 4 Downloadable Samples
- Illumina HiSeq 2000
Description
Complete polarization of macrophages towards an M1-like proinflammatory and antimicrobial state requires combined action of IFN-? and LPS. Synergistic activation of canonical inflammatory NF-?B target genes by IFN-? and LPS is well appreciated, but less is known about whether IFN-? negatively regulates components of the LPS response, and how this affects polarization. A combined transcriptomic and epigenomic approach revealed that IFN-? selectively abrogates LPS-induced feedback and select metabolic pathways by suppressing TLR4-mediated activation of gene enhancers. In contrast to superinduction of inflammatory genes via enhancers that harbor IRF sequences and bind STAT1, IFN-?-mediated repression targeted enhancers with STAT sequences that bound STAT3. TLR4-activated IFN-?-suppressed enhancers comprised two subsets distinguished by differential regulation of histone acetylation and recruitment of STAT3, CDK8 and cohesin, and were functionally inactivated by IFN-?. These findings reveal that IFN-? suppresses feedback inhibitory and metabolic components of the TLR response to achieve full M1 polarization, and provide insights into mechanisms by which IFN-? selectively inhibits TLR4-induced transcription. Overall design: RNA-seq analysis of transcriptional changes in human macrophages that were cultured with or without IFN-? and then stimulated with LPS
Publication Title
IFN-γ selectively suppresses a subset of TLR4-activated genes and enhancers to potentiate macrophage activation.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression analysis of freshly isolated CD14+ human monocytes and monocytes cultured in the presence or absence of interferon (IFN) -gamma for 24 h and then stimulated with Pam3Cys, a Toll-like receptor (TLR) 2 ligand, for 6 h. Results provide insight into mechanisms by which IFN-gamma reprograms early macrophage differentiation and subsequent response to TLR ligands.
Publication Title
Integrated regulation of Toll-like receptor responses by Notch and interferon-gamma pathways.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Macrophages from RA synovial fluids were compared to primary human monocyte-derived macrophages.
Publication Title
Interferon-γ Represses M2 Gene Expression in Human Macrophages by Disassembling Enhancers Bound by the Transcription Factor MAF.
Sample Metadata Fields
Specimen part, Disease stage, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
The discovery of activity-dependent neuroprotective protein (ADNP) regulated tooth eruption in mice and man, provides, for the first time, an early detection of tooth eruption, with full or almost full mouth of teeth at one year of age, as a potential biomarker for an intellectual disability (ID)/autism spectrum disorder (ASD) syndrome, toward improved translational medicine. Overall design: RNAseq of 4 samples, comparing three ADNP-mutated lymphoblastoid cell lines (LCLs, derived from ADNP-mutated children) with a non-mutated cell line. No replicates were performed but results were verified usign RT-PCR.
Publication Title
Tauopathy in the young autistic brain: novel biomarker and therapeutic target.
Sample Metadata Fields
Specimen part, Cell line, 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