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GSE49439
Homo sapiens
12 Downloadable Samples
Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In this work, we isolated and characterized a novel cell population derived from human amniotic fluid cells (hAKPC-P), and we differentiated them into podocytes.
Publication Title
A novel source of cultured podocytes.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
Illumina HiSeq 2500
Description
Posttranscriptional regulation of mRNA levels in neutrophils and its consequences for immune responses are unexplored. By employing profiling of the neutrophil transcriptome we show that the mRNA-destabilizing protein tristetraprolin (TTP) limits the expression of hundreds of genes, including genes negatively regulating apoptosis. Elicited TTP-deficient neutrophils exhibited reduced apoptosis and were increased in numbers. The anti-apoptotic protein Mcl-1 was elevated in TTP-deficient neutrophils and Mcl1 mRNA was bound and destabilized by TTP. Ablation of TTP in macrophages and neutrophils resulted in an improved defense and survival of mice during invasive infection with Streptococcus pyogenes. Mice lacking myeloid TTP prevented dissemination of bacteria and efficiently blunted systemic disease by massive but controlled neutrophil deployment. These data identify posttranscriptional control by TTP to restrict neutrophils and antimicrobial defense. Overall design: WT and TTPKO peritoneal neutrophils stimulated with LPS for 4 h. Each condition analyzed in three replicates
Publication Title
The RNA-binding protein tristetraprolin schedules apoptosis of pathogen-engaged neutrophils during bacterial infection.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 42 Downloadable Samples
- Illumina HiSeq 2500
Description
Precise control of mRNA decay is fundamental for robust yet not exaggerated inflammatory responses to pathogens. Parameters determining the specificity and extent of mRNA degradation within the entire inflammation-associated transcriptome remain incompletely understood. Using transcriptome-wide high resolution occupancy assessment of the mRNA-destabilizing protein TTP, a major inflammation-limiting factor, we qualitatively and quantitatively characterize TTP binding positions and functionally relate them to TTP-dependent mRNA decay in immunostimulated macrophages. We identify pervasive TTP binding with incompletely penetrant linkage to mRNA destabilization. A necessary but not sufficient feature of TTP-mediated mRNA destabilization is binding to 3’ untranslated regions (UTRs). Mapping of binding positions of the mRNA-stabilizing protein HuR in activated macrophages revealed that TTP and HuR binding sites in 3’ UTRs occur mostly in different transcripts implicating only a limited co-regulation of inflammatory mRNAs by these proteins. Remarkably, we identify robust and widespread TTP binding to introns of stable transcripts. Nuclear TTP is associated with spliced-out introns and maintained in the nucleus throughout the inflammatory response. Our study establishes a functional annotation of binding positions dictating TTP-dependent mRNA decay in immunostimulated macrophages. The findings allow navigating the transcriptome-wide landscape of RNA elements controlling inflammation. Overall design: Experiment comparing RNA decay rates in WT and TTP-/- macrophages at LPS 3 h and 6 h. Transcription was blocked with actinomycin D for 0, 45 or 90 min. Decay rates was calculated using linear model.
Publication Title
Tristetraprolin binding site atlas in the macrophage transcriptome reveals a switch for inflammation resolution.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Mus musculus
- 2 Downloadable Samples
- Illumina HiSeq 2000
Description
Precise control of mRNA decay is fundamental for robust yet not exaggerated inflammatory responses to pathogens. Parameters determining the specificity and extent of mRNA degradation within the entire inflammation-associated transcriptome remain incompletely understood. Using transcriptome-wide high resolution occupancy assessment of the mRNA-destabilizing protein TTP, a major inflammation-limiting factor, we qualitatively and quantitatively characterize TTP binding positions and functionally relate them to TTP-dependent mRNA decay in immunostimulated macrophages. We identify pervasive TTP binding with incompletely penetrant linkage to mRNA destabilization. A necessary but not sufficient feature of TTP-mediated mRNA destabilization is binding to 3’ untranslated regions (UTRs). Mapping of binding positions of the mRNA-stabilizing protein HuR in activated macrophages revealed that TTP and HuR binding sites in 3’ UTRs occur mostly in different transcripts implicating only a limited co-regulation of inflammatory mRNAs by these proteins. Remarkably, we identify robust and widespread TTP binding to introns of stable transcripts. Nuclear TTP is associated with spliced-out introns and maintained in the nucleus throughout the inflammatory response. Our study establishes a functional annotation of binding positions dictating TTP-dependent mRNA decay in immunostimulated macrophages. The findings allow navigating the transcriptome-wide landscape of RNA elements controlling inflammation. Overall design: RNA-Seq of RNA isolated from murine bone marrow derived macrophages (WT or TTP-deficient) stimulated for 6 h with LPS
Publication Title
Tristetraprolin binding site atlas in the macrophage transcriptome reveals a switch for inflammation resolution.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Controlled decay of cytokine and chemokine mRNAs restrains the time and amplitude of inflammatory responses. Tristetraprolin (TTP) binds to AU-rich elements in 3 untranslated regions of mRNA and targets the bound mRNA for degradation. We have addressed here the function of TTP in balancing the macrophage activation state by a comprehensive analysis of TTP-dependent mRNA decay in LPS-stimulated macrophages from WT and TTP-deficient mice.
Publication Title
Tristetraprolin-driven regulatory circuit controls quality and timing of mRNA decay in inflammation.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Up to now the role of tumor-specific pTregs and anergic cells during tumor development is not fully understood. Here we used a genetically-induced tumor expressing a MHC-II restricted DBY model antigen to characterize the tumor-induced pTregs and anergic cells that arise early during tumor development.
Publication Title
Induction of anergic or regulatory tumor-specific CD4<sup>+</sup> T cells in the tumor-draining lymph node.
Sample Metadata Fields
Time
View Samples- Mus musculus
- 15 Downloadable Samples
- Affymetrix Mouse Gene 2.1 ST Array (mogene21st)
Description
Up to know CD4 T cell antitumor responses have been mostly studied in transplanted tumor models. However, although they are valuable tools, they are not suitable to study the long term interactions between tumors and the immune system
Publication Title
Induction of anergic or regulatory tumor-specific CD4<sup>+</sup> T cells in the tumor-draining lymph node.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Gene 2.1 ST Array (hugene21st)
Description
CD4+ T cells as mediators of antitumor responses are beginning to be appreciated. Our team demonstrated that chronically activated CD4+ T cells (chCD4+ T cells) were expanded in the blood of cancer patients and their expansion is correlated with tumor regression.
Publication Title
Induction of anergic or regulatory tumor-specific CD4<sup>+</sup> T cells in the tumor-draining lymph node.
Sample Metadata Fields
Disease
View Samples- Arabidopsis thaliana
- 8 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
To identify genes associated with the heat stress (HS) memory, transcript profiling using Affymetrix ATH1 microarrays was performed to compare Col-0 seedlings after the priming stimulus with control plants (unprimed).
Publication Title
The plastid metalloprotease FtsH6 and small heat shock protein HSP21 jointly regulate thermomemory in Arabidopsis.
Sample Metadata Fields
Specimen part
View Samples- Populus trichocarpa
- 347 Downloadable Samples
- Illumina Genome Analyzer IIx, Illumina HiSeq 2000
Description
We transformed Populus trichocarpa and generated transgenics with knockdown or overexpression of monolignol genes and transcription factors Overall design: RNAseq of xylem tissue of transgenic and wildtype Populus trichocarpa. 378 samples.
Publication Title
Modeling cross-regulatory influences on monolignol transcripts and proteins under single and combinatorial gene knockdowns in Populus trichocarpa.
Sample Metadata Fields
Specimen part, Subject
View Samples