Filters
Technology
Platform
SRP017333
Mus musculus
4 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Background: Dendritic cells (DCs) are critical for regulating CD4 and CD8 T cell immunity, controlling Th1, Th2, and Th17 bias, generating inducible Tregs, and inducing tolerance. Multiple DC subsets have been identified in the mouse that are thought to have evolved to control these different immune outcomes. However, how these subsets differentially respond to inflammatory and/or tolerogenic signals in order to accomplish their divergent functionality remains unclear. Results: We analysed the responses of murine, splenic CD8 and CD11b DC subsets to in-vivo stimulation with lipopolysaccharide using RNA-Seq and systems biology approaches and observed responses are highly subset-specific. We reanalysed multiple datasets from the literature and show that these subset responses are obscured when analysing signaling at the population level. We show that the subset-specificity is due to the unique regulation of distinct TLR4 pathway modulators that ‘fine-tune’ a common TLR4 cascade rather and not due to major differences in signaling pathways or transcription factors. Conclusions: We propose the Pathway Modulation Model wherein common signaling pathways are regulated by unique sets of modulators allowing for distinct immune responses in closely related DC subsets. We extend these observations using analagous datasets from the literature and show that our model provides a global mechanism for generating cell subset-specific signaling in multiple subpopulations in mouse and man. Overall design: Splenic CD8 and CD11b DC subsets from LPS stimulated (10 pooled animals) and Control (5 pooled animals) mice were analysed by RNA-Seq.
Publication Title
A systems biology approach to the analysis of subset-specific responses to lipopolysaccharide in dendritic cells.
Sample Metadata Fields
Specimen part, Cell line, Subject, Time
View Samples- Danio rerio
- 18 Downloadable Samples
Affymetrix Zebrafish Genome Array (zebrafish)
Description
The goal of the project was to isolate single miRNA-expressing cells labelled by GFP reporter genes under the control of endogenous miRNA promoters and analyze expression levels of miRNA target genes in these cells. GFP-positive miRNA-expressing cells and GFP-negative cells from the rest of the embryos were purified at the same developmental stage to the cellular resolution using fluorescent activated cell sorting (FACS). Focus was on regulation by miR-206 and miR-133 in the developing somites and miR-124 in the developing central nervous system. Comparison of wild-type embryos and those lacking miRNAs revealed predicted
Publication Title
Coherent but overlapping expression of microRNAs and their targets during vertebrate development.
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 14 Downloadable Samples
- IlluminaGenomeAnalyzerII, IlluminaHiSeq2000
Description
The post-transcriptional fate of messenger RNAs (mRNAs) is largely dictated by their 3'' untranslated regions (3''UTRs), which are defined by cleavage and polyadenylation (CPA) of pre-mRNAs. We used poly(A)-position profiling by sequencing (3P-Seq) to map poly(A) sites at eight developmental stages and tissues in the zebrafish. Analysis of over 60 million 3P-Seq reads substantially increased and improved existing 3''UTR annotations, resulting in confidently identified 3''UTRs for more than 78.79% of the annotated protein-coding genes in zebrafish. Most zebrafish genes undergo alternative CPA with more than a thousand genes using different dominant 3''UTRs at different stages. 3''UTRs tend to be shortest in the ovaries and longest in the brain. Isoforms with some of the shortest 3''UTRs are highly expressed in the ovary yet absent in the maternally contributed RNAs of the embryo, perhaps because their 3''UTRs are too short to accommodate a uridine-rich motif required for stability of the maternal mRNA. At two hours post-fertilization, thousands of unique poly(A) sites appear at locations lacking a typical polyadenylation signal, which suggests a wave of widespread cytoplasmic polyadenylation of mRNA degradation intermediates. Our insights into the identities, formation, and evolution of zebrafish 3''UTRs provide a resource for studying gene regulation during vertebrate development. Overall design: 3P-Seq was used to map the 3'' ends of protein-coding genes in the zebrafish genome
Publication Title
Extensive alternative polyadenylation during zebrafish development.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 55 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
MiRNAs are essential mediators of many biological processes. The aim of this study was to investigate the dynamics of miRNA-mRNA regulatory networks during exercise and subsequent recovery period.
Publication Title
Dynamically regulated miRNA-mRNA networks revealed by exercise.
Sample Metadata Fields
Sex, Age
View Samples- Homo sapiens
- 114 Downloadable Samples
Affymetrix Human Genome U219 Array (hgu219), Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
In this paper we demonstrated the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery
Publication Title
Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U219 Array (hgu219), Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
In this paper we demonstrated the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery
Publication Title
Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
In this paper we demonstrated the potential to flag toxicity issues by utilizing data from exploratory experiments which are typically generated for target evaluation purposes during early drug discovery
Publication Title
Using transcriptomics to guide lead optimization in drug discovery projects: Lessons learned from the QSTAR project.
Sample Metadata Fields
Cell line, Treatment
View Samples- Homo sapiens
- 20 Downloadable Samples
- IlluminaHiSeq2500
Description
Purpose: We have identified a new compound (1C8) that inhibits HIV-1 replication and that displays very low cellular toxicity. Here, we assess the molecular mechanisms of action of 1C8. Following transcription of the HIV-1 genome, its primary transcript is processed to produce dozens of distinct mRNAs through the alternative use of splice sites. Results: 1C8 decreases the activity of SRSF10, a cellular protein that controls the selection of splice sites in HIV-1 transcripts. 1C8 decreases the phosphorylation of SRSF10, and this change is associated with alterations in the interaction of SRSF10 with HIV-1 transcripts and factors that control splice site selection. Thus, 1C8 represents a novel compound with properties that are potentially useful for treating HIV-1 infection. Overall design: Examination of RNA-seq to investigate alternative splicing changes between control and 4 different concentrations of a drug that 1C8. 4 replicates were sequenced for each condition.
Publication Title
Modulation of the splicing regulatory function of SRSF10 by a novel compound that impairs HIV-1 replication.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The human prostate epithelium is predominantly comprised of two cell-types: basal and luminal. While basal cells exhibit significant progenitor activity in a variety of functional assays, luminal cells are depleted of this activity. Recent studies indicate that approximately 1% of luminal cells exhibit progenitor activity. We have discovered that differential expression of the glycoprotein CD38 can fractionate the luminal population into two subsets: CD38+ and CD38-low. In functional assays, the CD38-low luminal cells exhibit roughly 5-fold increased progenitor activity compared to the remaining CD38+ population. Therefore, we propose that CD38-low luminal cells represent an enriched luminal progenitor population while the CD38+ subset is predominantly comprised of mature non-progenitor luminal cells.
Publication Title
Low CD38 Identifies Progenitor-like Inflammation-Associated Luminal Cells that Can Initiate Human Prostate Cancer and Predict Poor Outcome.
Sample Metadata Fields
Specimen part, Subject
View Samples