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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
- 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- 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- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2500
Description
IL-17-producing CD8+ (Tc17)T cells are implicated in the pathogenesis of multiple sclerosis (MS), thereby representing a promising target for therapy. We found that dimethyl fumarate (DMF), a first-line medication for MS upregulated reactive oxygen species (ROS) by glutathione depletion in murine Tc17 cells, which limited IL-17 and diverted Tc17 cells towards cytotoxic T lymphocyte (CTL) signature. DMF enhanced PI3K-AKT-FOXO1-T-bet- as well as STAT5-signaling leading to restricted permissive histone state at the Il17 locus. T-bet-deficiency, inhibiting PI3K-AKT, STAT5 or histone deacetylases prevented DMF-ROS-mediated IL-17 suppression. In MS patients with stable response, DMF suppressed IL-17 production by CD8+ T-cells and triggered diversion from Tc17 towards CTL signature along with enriched ROS-, PI3K-AKT-FOXO1-signaling, demonstrating comparable regulation across species. Accordingly, in the mouse model for MS, DMF limited Tc17-encephalitogenicity. Our findings disclose DMF-ROS-AKT-driven pathway, which selectively modulates Tc17 fate to ameliorate MS, thus opening avenue to develop markers and targets for specific therapy. Overall design: Examination of DMF-induced expression changes in 3 conditions, 3 samples each: murine TC17 cells without treatment as control group, murine Tc17 cells treated with DMF and murine Tc17 cells treated with DMF and Glutathione(GSH)
Publication Title
IL-17<sup>+</sup> CD8<sup>+</sup> T cell suppression by dimethyl fumarate associates with clinical response in multiple sclerosis.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
IL-17-producing CD8+ (Tc17)T cells are implicated in the pathogenesis of multiple sclerosis (MS), thereby representing a promising target for therapy. We found that dimethyl fumarate (DMF), a first-line medication for MS upregulated reactive oxygen species (ROS) by glutathione depletion in murine Tc17 cells, which limited IL-17 and diverted Tc17 cells towards cytotoxic T lymphocyte (CTL) signature. DMF enhanced PI3K-AKT-FOXO1-T-bet- as well as STAT5-signaling leading to restricted permissive histone state at the Il17 locus. T-bet-deficiency, inhibiting PI3K-AKT, STAT5 or histone deacetylases prevented DMF-ROS-mediated IL-17 suppression. In MS patients with stable response, DMF suppressed IL-17 production by CD8+ T-cells and triggered diversion from Tc17 towards CTL signature along with enriched ROS-, PI3K-AKT-FOXO1-signaling, demonstrating comparable regulation across species. Accordingly, in the mouse model for MS, DMF limited Tc17-encephalitogenicity. Our findings disclose DMF-ROS-AKT-driven pathway, which selectively modulates Tc17 fate to ameliorate MS, thus opening avenue to develop markers and targets for specific therapy. Overall design: CD8+ memory cells from human blood
Publication Title
IL-17<sup>+</sup> CD8<sup>+</sup> T cell suppression by dimethyl fumarate associates with clinical response in multiple sclerosis.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 132 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The ability to dissect heterogeneity in colorectal cancer (CRC) is a critical step in developing predictive biomarkers. The goal of this study was to develop a gene expression based molecular subgrouping model, which predicts the likelihood that patients will respond to specific therapies.
Publication Title
Activation of the mTOR Pathway by Oxaliplatin in the Treatment of Colorectal Cancer Liver Metastasis.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 66 Downloadable Samples
- Illumina HiSeq 2000
Description
Purpose: Identify differentially expressed genes in placental samples from early-onset (EO) IUGR, EO-PE, as well as pregnancies complicated by both EO-PE and EO-IUGR Overall design: Methods: Isolated total RNA from human placenta at birth and used it for RNA-sequencing on the Hiseq2000. Sequences were aligned to the human transcriptome (hg19/genome_build37) . Aligned sequences were then used to obtain abundance measurements and conduct differential expression analysis.
Publication Title
Placental microRNAs in pregnancies with early onset intrauterine growth restriction and preeclampsia: potential impact on gene expression and pathophysiology.
Sample Metadata Fields
Specimen part, Subject
View Samples- Vitis vinifera
- 174 Downloadable Samples
- Affymetrix Vitis vinifera (Grape) Genome Array (vitisvinifera)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Alignment of time course gene expression data and the classification of developmentally driven genes with hidden Markov models.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 53 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We studied intragraft gene expression profiles of positive crossmatch (+XM) kidney transplant recipients who develop transplant glomerulopathy (TG) and those who do not. Whole genome microarray analysis and quantitative rt-PCR for 30 transcripts were performed on RNA from protocol renal allograft biopsies in 3 groups: 1) +XM/TG+ biopsies before and after TG; 2) +XM/NoTG; and 3) negative crossmatch kidney transplants (control). Microarray comparisons showed few differentially expressed genes between paired biopsies from +XM/TG+ recipients before and after the diagnosis of TG. Comparing +XM/TG+ and control groups, significantly altered expression was seen for 2,447 genes (18%) and 3,200 genes (24%) at early and late time points, respectively. Canonical pathway analyses of differentially expressed genes showed inflammatory genes associated with innate and adaptive immune responses. Comparing +XM/TG+ and +XM/NoTG groups, 3,718 probe sets were differentially expressed but these were over-represented in only 4 pathways. A classic accommodation phenotype was not identified. Using rt-PCR, the expression of inflammatory genes was significantly increased in +XM/TG+ recipients compared to control biopsies and to +XM/NoTG biopsies. In conclusion, pre-transplant DSA results in a gene expression profile characterized by inflammation and cellular infiltration and the majority of XM+ grafts are exposed to chronic injury.
Publication Title
Intragraft gene expression in positive crossmatch kidney allografts: ongoing inflammation mediates chronic antibody-mediated injury.
Sample Metadata Fields
Specimen part, Time
View Samples- Vitis vinifera
- 38 Downloadable Samples
- Affymetrix Vitis vinifera (Grape) Genome Array (vitisvinifera)
Description
Changes in gene expression during berry development during a grape growing season were analysed.
Publication Title
Alignment of time course gene expression data and the classification of developmentally driven genes with hidden Markov models.
Sample Metadata Fields
No sample metadata fields
View Samples