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SRP070703
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- Homo sapiens
- 910 Downloadable Samples
- Illumina HiSeq 2500
Description
Non-coding RNAs regulate many biological processes including neurogenesis. The brain-enriched miR-124 is assigned as a key player of neuronal differentiation via its complex, but little understood, regulation of thousands of annotated targets. To systematically chart its regulatory functions, we used CRISPR/Cas9 gene editing to disrupt all six miR-124 alleles in human stem cells. Upon neuronal induction, miR-124-depleted cells underwent neurogenesis and became functional neurons, albeit with altered morphology and neurotransmitter specification. By RNA-induced-silencing-complex precipitation, we found that other miRNA species were upregulated in miR-124 depleted neurons. Furthermore, we identified 98 miR-124 targets of which some directly led to decreased viability. We performed advanced transcription-factor-network analysis and revealed indirect miR-124 effects on apoptosis and neuronal subtype differentiation. Our data emphasizes the need for combined experimental- and systems-level analyses to comprehensively disentangle and reveal miRNA functions, including their involvement in the neurogenesis of diverse neuronal cell types found in the human brain. Overall design: RNA profile for timecourse of neuronal Neurogenin-1 and 2-triggered differentiation from human iPSCs (wildtype and ?miR-124).
Publication Title
Combined Experimental and System-Level Analyses Reveal the Complex Regulatory Network of miR-124 during Human Neurogenesis.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 93 Downloadable Samples
- Illumina HiSeq 2500
Description
Non-coding RNAs regulate many biological processes including neurogenesis. The brain-enriched miR-124 is assigned as a key player of neuronal differentiation via its complex, but little understood, regulation of thousands of annotated targets. To systematically chart its regulatory functions, we used CRISPR/Cas9 gene editing to disrupt all six miR-124 alleles in human stem cells. Upon neuronal induction, miR-124-depleted cells underwent neurogenesis and became functional neurons, albeit with altered morphology and neurotransmitter specification. By RNA-induced-silencing-complex precipitation, we found that other miRNA species were upregulated in miR-124 depleted neurons. Furthermore, we identified 98 miR-124 targets of which some directly led to decreased viability. We performed advanced transcription-factor-network analysis and revealed indirect miR-124 effects on apoptosis and neuronal subtype differentiation. Our data emphasizes the need for combined experimental- and systems-level analyses to comprehensively disentangle and reveal miRNA functions, including their involvement in the neurogenesis of diverse neuronal cell types found in the human brain. Overall design: RNA interacting protein immunoprecipitation with AGO2 for miR-124 target enrichment from neuronal Neurogenin-1 and 2-triggered differentiation from human iPSCs (wildtype and ?miR-124) and subsequent sequencing.
Publication Title
Combined Experimental and System-Level Analyses Reveal the Complex Regulatory Network of miR-124 during Human Neurogenesis.
Sample Metadata Fields
Subject
View Samples- Mus musculus
- 26 Downloadable Samples
Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
The dual bromodomain protein Brd2 is closely related to the basal transcription factor TAFII250, which is essential for cyclin A transactivation and mammalian cell cycle progression. In transgenic mice, constitutive lymphoid expression of Brd2 causes a malignancy most similar to human diffuse large B cell lymphoma. We compare the genome-wide transcriptional expression profiles of these lymphomas with those of proliferating and resting normal B cells. Transgenic tumors reproducibly show differential expression of a large number of genes important for cell cycle control and lymphocyte biology; expression patterns are either tumor-specific or proliferation-specific. Several of their human orthologs have been implicated in human lymphomagenesis. Others correlate with human disease survival time. BRD2 is underexpressed in some subtypes of human lymphoma and these subtypes display a number of similarities to the BRD2-mediated murine tumors. We illustrate with a high degree of detail that cancer is more than rampant cellular proliferation, but involves the additional transcriptional mobilization of many genes, some of them poorly characterized, which show a tumor-specific pattern of gene expression.
Publication Title
Tumor-specific and proliferation-specific gene expression typifies murine transgenic B cell lymphomagenesis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 97 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Genomic and expression profiling using 38K BAC array-CGH and Illumina HT-12 beadchips were performed on 97 diploid invasive breast tumors to assess the impact of gene dosage on gene expression patterns and the effect of other mechanisms on transcriptional levels. Patient stratification was performed according to axillary lymph node status (node-negative, pN0; node-positive, pN1) and overall survival (>8-year survivors; breast cancer-specific mortality within 8 years of diagnosis). Array-CGH results was validated by FISH using tumors showing HER2/neu gene amplification and expression profiling was confirmed using qPCR for 16 transcripts.
Publication Title
Clinical implications of gene dosage and gene expression patterns in diploid breast carcinoma.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 97 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Genomic and expression profiling using 38K BAC array-CGH and Illumina HT-12 beadchips were performed on 97 diploid invasive breast tumors to assess the impact of gene dosage on gene expression patterns and the effect of other mechanisms on transcriptional levels. Patient stratification was performed according to axillary lymph node status (node-negative, pN0; node-positive, pN1) and overall survival (>8-year survivors; breast cancer-specific mortality within 8 years of diagnosis). Array-CGH results was validated by FISH using tumors showing HER2/neu gene amplification and expression profiling was confirmed using qPCR for 16 transcripts.
Publication Title
Clinical implications of gene dosage and gene expression patterns in diploid breast carcinoma.
Sample Metadata Fields
Disease, Disease stage
View Samples- Homo sapiens
- 53 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Transcriptomic profiling of human breast tumors.
Publication Title
Clinical implications of gene dosage and gene expression patterns in diploid breast carcinoma.
Sample Metadata Fields
Age, Specimen part
View Samples- Macaca fascicularis
- 23 Downloadable Samples
- Affymetrix Human Genome U95 Version 2 Array (hgu95av2)
Description
Liver gene expression was examined in male cynomolgus monkeys treated with ciprofibrate (PPAR-alpha agonist) for 4 days at 400 mg/kg/day and treated for 15 days at 0, 3, 30, 150 or 400 mg/kg/day. The untreated control group were given only the vehicle (0.5% hydroxypropyl methylcellulose). Two animals per group were used for the 4 day treatment and four animals per group were used for the 15 day treatment (except the 15 day control group, which had three animals). Selection of significantly changed probesets was done using Rosetta Resolver and the fold-change and p values as determined by Resolver are given below. Affymetrix CEL files and MAS5-processed data have been made availabe for convenience. Note that data processing reported in the Toxicological Sciences manuscript was done using Rosetta Resolver and the treated versus control group fold-change and p-value are appended to the Series entry. An article has been published in Toxicological Sciences regarding this dataset; the data interpretation was based on the Rosetta Resolver data.
Publication Title
Gene expression profiling of the PPAR-alpha agonist ciprofibrate in the cynomolgus monkey liver.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 16 Downloadable Samples
- Illumina HiSeq 2000
Description
A multitude of genes have been associated with bipolar disorder via SNP genotyping studies. However, many of these associated SNPs are found within intronic or intergenic regions of the human genome. We were interested in studying transcriptional profiles/splice variation of genes associated with bipolar disorder within the human striatum. Understanding how these associated genes are transcribed in the human brain may help to guide the development of therapeutic agents for the treatment of bipolar disorder and other neuropsychiatric illnesses. Overall design: NEBNext Ultra Directional RNAseq libraries were generated from putamen and caudate nucleus tissues from 4 healthy control individuals and 4 individuals with bipolar disorder. These libraries were then multiplexed and run on an Illumina HiSeq platform using single read 100bp chemistries.
Publication Title
Novel PDE10A transcript diversity in the human striatum: Insights into gene complexity, conservation and regulation.
Sample Metadata Fields
Specimen part, Disease stage, Subject
View Samples