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SRP069880
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
- 1 Downloadable Sample
Description
The hallmark of the cerebral neocortex is its organization into six distinct layers, each containing a characteristic set of neural cell types and synaptic connections. The transcriptional events involved in laminar development and function still remain elusive. Here we employed deep sequencing of mRNA and small RNA species to gain insights into transcriptional differences among layers and their temporal dynamics during postnatal development of the mouse primary somatosensory neocortex. A number of novel coding and noncoding transcripts were identified with specific spatiotemporal expression and splicing patterns across layers or time points. We also identified gene co-expression networks associated with distinct biological processes and transcriptional sharing between distinct biological processes, as well as, potential microRNA and mRNA interactions. Overall, this study provides an integrated view of the laminar and temporal expression dynamics of coding and noncoding transcripts in the mouse neocortex and a resource for future studies of neurodevelopment and transcriptome.
Publication Title
Laminar and temporal expression dynamics of coding and noncoding RNAs in the mouse neocortex.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 10 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene expression from pre- and post- Cediranib treated patients with metastatic Alveolar Soft Part Sarcoma (ASPS)
Publication Title
Cediranib for metastatic alveolar soft part sarcoma.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Homo sapiens
- 18 Downloadable Samples
- Illumina HumanHT-12 V4.0 expression beadchip
Description
We surveyed RNA-Seq data to identify those TEs that are transcriptionally active uniquely in human pluripotent cells. We identified one endogenous retrovirus (HERV-H) family, uniquely found in primates as being unusually abundant in the transcriptome. The microarray data provided is to support our human naive cell hypothesis.
Publication Title
Primate-specific endogenous retrovirus-driven transcription defines naive-like stem cells.
Sample Metadata Fields
Sex, Cell line
View Samples