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SRP079900
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- 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- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Gene expression changes in mouse skeletal muscle were assessed in wild-type and Jhdm2a null skeletal muscle in an effort to define the role of Jhdm2a in energy expenditure and metabolism.
Publication Title
Role of Jhdm2a in regulating metabolic gene expression and obesity resistance.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 32 Downloadable Samples
- Illumina HiSeq 2000
Description
Natural killer T (NKT) cells identified by CD1d-tetramer and TCRb were isolated from the thymi of wild type and Ezh2 knockout mice. The NKT cells were FACS sorted into different stages based on the surface expression of CD44 and NK1.1. Overall design: For both wildtype and knockout mice, RNA was extracted from two biological replicates of CD44+ NK1.1- cells, one replicate of CD44+ NK1.1+ cells and one replicate of CD44- NK1.1- cells. Each RNA sample was divided into four and sequenced on four lanes of an Illumina HiSeq sequencer.
Publication Title
A non-canonical function of Ezh2 preserves immune homeostasis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina Genome Analyzer
Description
To understand CD8 effector T cell differentiation in more detial we have used transcriptional profiling of antigen-specific CD8 T cells deficient in Blimp1, IL-2ra, or both, or Tbet. We reveal a common program of effector differentiation regulated by cytokine signaling and the combined activities of Blimp1 and T-bet, indicating remarkable redundancy and specificity in the control of genes involved in the differentiation of effector T cells. Overall design: Bone marrow chimeric mice were generated containing congenically marked wildtype and mutant heamatopoietic cells. The mice were infected with primed with PR8 influenza virus. Six weeks later they were infected with the heterologous HKx31 influenza virus. Antigen-specific (NP366) positive CD8 T cells were sorted. RNA was exracted and RNA sequening performed.
Publication Title
A molecular threshold for effector CD8(+) T cell differentiation controlled by transcription factors Blimp-1 and T-bet.
Sample Metadata Fields
No sample metadata fields
View Samples- 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- Mus musculus
- 6 Downloadable Samples
- Illumina Genome Analyzer
Description
To understand the differentiation of effector Tregs in more detail, we have performed transcriptional profiling of central Tregs and effector Tregs, based on Blimp1 expression. We performed RNA-sequencing of Foxp3+ regulatory T cells, comparing Blimp1/GFP+ and Blimp1/GFP- cells Overall design: Three biologically independent samples for each condition were sequenced (condition 1: CD4+ CD25high Blimp1/GFP+; condition 2: CD4+ CD25high Blimp1/GFP-); cells were sorted from pooled spleens and lymphnodes of Blimp1/GFP reporter mice
Publication Title
The transcriptional regulators IRF4, BATF and IL-33 orchestrate development and maintenance of adipose tissue-resident regulatory T cells.
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- Zea mays
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
We performed a transcriptomic analysis to identify genes differentially transcribed in the maize stem upon corn borer feeding and treatment with insects regurgitates by using the MACE (Massive Analysis of cDNA Ends) technology. Overall design: Two comparisons were performed: Insect chewing vs control and Regurgitate+wounding vs wounding in three biological replicates per treatment
Publication Title
Maize Stem Response to Long-Term Attack by <i>Sesamia nonagrioides</i>.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Mus musculus
- 2 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Genome-wide uH2A localization analysis highlights Bmi1-dependent deposition of the mark at repressed genes.
Sample Metadata Fields
Sex
View Samples