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GSE11327
Homo sapiens
8 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pro-inflammation triggered by microbial lipopolysaccharide (LPS) through Toll-like receptor (TLR) 4 in the presence of interferon (IFN)-g induces cytokine secretion in dendritic cells (DCs) tightly regulated by a defined differentiation program. This DC differentiation is characterized by a dynamic immune activating but also tolerance inducing phenotype associated with irreversible down-modulation of cytokines. CD40L on activated T cells further modifies DC differentiation. Using DNA micro arrays we showed down-regulated mRNA levels of TLR signaling molecules while CD40/CD40L signaling molecules were up-regulated at a time when LPS/IFN-g activated DCs have ceased cytokine expression. Accordingly we demonstrated that CD40/CD40L but not TLR4 or TLR3 signaling mediated by LPS or poly (cytidylic-inosinic) acid (poly I:C) and dsRNA re-established the capacity to secret interleukin (IL)-12 in LPS/IFN-g activated DCs, which have exhausted their potential for cytokine secretion. This resulting TH1 polarizing DC phenotype which lacked accompanying secretion of the crucial immune suppressive IL-10 - enhanced activation of cytotoxic T lymphocytes (CTLs). We therefore conclude that immune modulation is restricted to a secondary T-cell mediated stimulus at an exhausted DC state which prevents an immune tolerant DC phenotype. These findings impacts on the rational design of TLR activated DC-based cancer vaccines for the induction of anti-tumoral CTL responses.
Publication Title
CD40 ligation restores type 1 polarizing capacity in TLR4-activated dendritic cells that have ceased interleukin-12 expression.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 6 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Genome-wide transcriptome analyses have allowed for systems- level insights into gene regulatory networks. Due to the limited depth of quantitative proteomics, however, our understanding of post-transcriptional gene regulation and its effects on protein complex stoichiometry are lagging behind. Here, we employ deep sequencing and iTRAQ technology to determine transcript and protein expression changes of a Drosophila brain tumour model at near genome-wide resolution. In total, we quantify more than 6,200 tissue-specific proteins, corresponding to about 70% of all transcribed protein-coding genes. Using our integrated data set, we demonstrate that post-transcriptional gene regulation varies considerably with biological function and is surprisingly high for genes regulating transcription. We combine our quantitative data with protein-protein interaction data and show that post-transcriptional mechanisms significantly enhance co-regulation of protein complex subunits beyond transcriptional co-regulation. Interestingly, our results suggest that only about 11% of the annotated Drosophila protein complexes are co-regulated in the brain. Finally, we refine the composition of some of these core protein complexes by analysing the co-regulation of potential subunits. Our comprehensive transcriptome and proteome data provide a rich resource for quantitative biology and offer novel insights into understanding post- transcriptional gene regulation in a tumour model. Overall design: Transcriptomes of 1-3 day old adult female Drosophila melanogaster heads of control and brat mutant were generated by deep sequencing, in triplicate, using Illumina GAIIx.
Publication Title
Transcriptome and proteome quantification of a tumor model provides novel insights into post-transcriptional gene regulation.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 24 Downloadable Samples
- NextSeq 500
Description
Purpose:To systematically assess the differences between high-throughput single-cell and single-nuclei RNA-seq approaches, we compared Drop-seq and DroNc-seq, two microfluidic-based 3' RNA capture technologies that profile total cellular and nuclear RNA, respectively, during a time course experiment of human induced pluripotent stem cells (iPSCs) differentiating into cardiomyocytes Conclusions: Clustering of time-series transcriptomes from Drop-seq and DroNc-seq revealed six distinct cell types, five of which were found in both techniques. Furthermore, single-cell trajectories reconstructed from both techniques reproduced expected differentiation dynamics. Overall design: Drop-seq and DroNc-seq each on 2 hiPSC cell lines differentiating into cardiomyocytes across 5 time points. DroNc-seq on post-mortem primary heart tissue.
Publication Title
Systematic Comparison of High-throughput Single-Cell and Single-Nucleus Transcriptomes during Cardiomyocyte Differentiation.
Sample Metadata Fields
Specimen part, Disease, Subject, Time
View Samples- Homo sapiens
- 92 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Up-regulation of a HOXA-PBX3 homeobox-gene signature following down-regulation of miR-181 is associated with adverse prognosis in patients with cytogenetically abnormal AML.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 92 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Increased expression levels of miR-181 family members have been shown to be associated with favorable outcome in patients with cytogenetically normal acute myeloid leukemia. Here we show that increased expression of miR-181a and miR-181b is also significantly (P < .05; Cox regression) associated with favorable overall survival in cytogenetically abnormal AML (CA-AML) patients. We further show that up-regulation of a gene signature composed of 4 potential miR-181 targets (including HOXA7, HOXA9, HOXA11, and PBX3), associated with down-regulation of miR-181 family members, is an independent predictor of adverse overall survival on multivariable testing in analysis of 183 CA-AML patients. The independent prognostic impact of this 4-homeobox-gene signature was confirmed in a validation set of 271 CA-AML patients. Furthermore, our in vitro and in vivo studies indicated that ectopic expression of miR-181b significantly promoted apoptosis and inhibited viability/proliferation of leukemic cells and delayed leukemogenesis; such effects could be reversed by forced expression of PBX3. Thus, the up-regulation of the 4 homeobox genes resulting from the down-regulation of miR-181 family members probably contribute to the poor prognosis of patients with nonfavorable CA-AML. Restoring expression of miR-181b and/or targeting the HOXA/PBX3 pathways may provide new strategies to improve survival substantially.
Publication Title
Up-regulation of a HOXA-PBX3 homeobox-gene signature following down-regulation of miR-181 is associated with adverse prognosis in patients with cytogenetically abnormal AML.
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
In an attempt to gain insight into the mechanism whereby irradiated cells influence the outcome of DSB repair in their non-irradiated neighbors, we performed whole genome expression profiling.
Publication Title
Co-culturing with High-Charge and Energy Particle Irradiated Cells Increases Mutagenic Joining of Enzymatically Induced DNA Double-Strand Breaks in Nonirradiated Cells.
Sample Metadata Fields
Cell line
View Samples- Arabidopsis thaliana
- 24 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The first described feedback loop of the Arabidopsis circadian clock is based on reciprocal regulation between TOC1 and CCA1/LHY. CCA1 and LHY are MYB transcription factors that bind directly to the TOC1 promoter to negatively regulate its expression. Conversely, the activity of TOC1 has remained less well characterized. Genetic data supports that TOC1 is necessary for the reactivation of CCA1/LHY, but there is little description of its biochemical function. Here we show that TOC1 occupies specific genomic regions in the CCA1 and LHY promoters. Purified TOC1 binds directly to DNA through its CCT domain, which is similar to known DNA binding domains. Chemical induction and transient overexpression of TOC1 in Arabidopsis seedlings cause repression of CCA1/LHY expression demonstrating that TOC1 can repress direct targets, and mutation or deletion of the CCT domain prevents this repression showing that DNA binding is necessary for TOC1 action. Furthermore, we use the Gal4/UAS system in Arabidopsis to show that TOC1 acts as a general transcriptional repressor, and that repression activity is in the Pseudoreceiver (PR) domain of the protein. To identify the genes regulated by TOC1 on a genomic scale, we couple TOC1 chemical induction with microarray analysis and identify new potential TOC1 targets and output pathways. Together these results define the biochemical action of the core clock protein TOC1 and refine our perspective on how plant clocks function.
Publication Title
Arabidopsis circadian clock protein, TOC1, is a DNA-binding transcription factor.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 3 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Continuous regeneration of digestive enzyme (zymogen) secreting chief cells is a normal aspect of stomach function that is disrupted in pre-cancerous lesions. Regulation of zymogenic cell (ZC) differentiation is poorly understood. Here we profile Parietal, Pit, and Zymogenic cells for comparison and study.
Publication Title
The maturation of mucus-secreting gastric epithelial progenitors into digestive-enzyme secreting zymogenic cells requires Mist1.
Sample Metadata Fields
Specimen part
View Samples- Arabidopsis thaliana
- 23 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Transcript profiling analysis of csn3-1, csn4-1 and csn5 (csn5a-2 csn5b) light grown and dark grown mutant seedlings compared to light grown and dark grown wild type using Arabidopsis ATH1 GeneChip array
Publication Title
The Arabidopsis COP9 signalosome is essential for G2 phase progression and genomic stability.
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 12 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
The phytohormone GA controls multiple important developmental processes in plants such as germination, elongation growth and flowering time. In this experiment, we look for early GA response genes in 7 day-old light-grown Arabidopsis seedlings. To this end we compare four data sets: (1) a GA biosynthesis mutant ga-1 (SALK_109115) mock treated for 1 hr; (2) a GA biosynthesis mutant ga-1 (SALK_109115) treated for 1 hr with 100 M GA3; (3) a gid1a-1 gid1b-1 gid1c-2 GA receptor triple mutant mock treated for 1 hr; (4) a gid1a-1 gid1b-1 gid1c-2 GA receptor triple mutant treated for 1 hr with 100 M GA3. In a comparison of the two ga-1 samples, GA regulated genes can be identified, and the assumption is that bona fide GA regulated genes are not responding in the gid1a-1 gid1b-1 gid1c-2 GA receptor mutant.
Publication Title
The DELLA domain of GA INSENSITIVE mediates the interaction with the GA INSENSITIVE DWARF1A gibberellin receptor of Arabidopsis.
Sample Metadata Fields
No sample metadata fields
View Samples