Filters
Technology
Platform
GSE56681
Homo sapiens
19 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
The alarmins myeloid-related protein (MRP) 8 and MRP14 are the dominant cytoplasmic proteins in phagocytes. After release by activated phagocytes extracellular MRP8/MRP14 complexes promote inflammation in many diseases, including infections, allergies, autoimmune diseases, rheumatoid arthritis or inflammatory bowel disease. As receptors for the pro-inflammatory effects of human MRP8, the active component of the MRP8/MRP14-complex, Toll-like receptor (TLR) 4 and the multi-ligand receptor of advanced glycation end products (RAGE) are controversial discussed. Using a comparative bioinformatics analysis between genome-wide response patterns of monocytes to MRP8, endotoxin and different cytokines we demonstrated a dominant role of TLR4 during MRP8-mediated phagocyte activation. The relevance of this signaling pathway could be confirmed in independent cell models for TLR4 and RAGE dependent signaling in mouse and man. In addition to well-known proinflammatory functions of MRP8 our systems biology approach unraveled a novel anti-apoptotic effect of MRP8 on monocytes which was confirmed in independent functional experiments. Our data define the dominance of the TLR4-MRP8 axis in activation of human phagocytes which represents a novel attractive target for modulation of overwhelming innate immune responses.
Publication Title
Transcriptome assessment reveals a dominant role for TLR4 in the activation of human monocytes by the alarmin MRP8.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 26 Downloadable Samples
Illumina HiSeq 2000
Description
RNA editing is a mutational mechanism that specifically alters the nucleotide content in sets of transcripts while leaving their cognate genomic blueprint intact. Editing has been detected from bulk RNA-seq data in thousands of distinct transcripts, but apparent editing rates can vary widely (from under 1% to almost 100%). These observed editing rates could result from approximately equal rates of editing within each individual cell in the bulk sample, or alternatively, editing estimates from a population of cells could reflect an average of distinct, biologically significant editing signatures that vary substantially between individual cells in the population. To distinguish between these two possibilities we have constructed a hierarchical Bayesian model which quantifies the variance of editing rates at specific sites using RNA-seq data from both single cells and a cognate bulk sample consisting of ~ 106 cells. The model was applied to data from murine bone-marrow derived macrophages and dendritic cells, and predicted high variance for specific edited sites in both cell types tested. We then 1 validated these predictions using targeted amplification of specific editable transcripts from individual macrophages. Our data demonstrate substantial variance in editing signatures between single cells, supporting the notion that RNA editing generates diversity within cellular populations. Such editing-mediated RNA-level sequence diversity could contribute to the functional heterogeneity apparent in cells of the innate immune system. Overall design: 26 samples were subjected to RNA-seq: 24 single WT macrophages, and 2 bulk samples (Apobec1 WT and KO macrophages), consisting of 500,000-1 million cells each.
Publication Title
RNA editing generates cellular subsets with diverse sequence within populations.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Bos taurus
- 9 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Assessment of the putative differential gene expression profiles in high osmolality-treated bovine nucleus pulposus intervertebral disc cells for a short (5 h) and a long (24 h) time period. Identification of novel genes up- or down-regulated as an early or a late response to hyperosmotic stress.
Publication Title
Deficiency in the α1 subunit of Na+/K+-ATPase enhances the anti-proliferative effect of high osmolality in nucleus pulposus intervertebral disc cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 25 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The metabolic syndrome (MetS) is characterized by the presence of metabolic abnormalities that include abdominal obesity, dyslipidemia, hypertension, increased blood glucose/insulin resistance, hypertriglyceridemia and increased risk for cardiovascular disease (CVD). The ApoE*3Leiden.human Cholesteryl Ester Transfer Protein (ApoE3L.CETP) mouse model manifests several features of the MetS upon high fat diet (HFD) feeding. Moreover, the physiological changes in the white adipose tissue (WAT) contribute to MetS comorbidities. The aim of this study was to identify transcriptomic signatures in the gonadal WAT of ApoE3L.CETP mice in discrete stages of diet-induced MetS.
Publication Title
Transcriptome analysis of the adipose tissue in a mouse model of metabolic syndrome identifies gene signatures related to disease pathogenesis.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 51 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Cellular Differentiation of Human Monocytes Is Regulated by Time-Dependent Interleukin-4 Signaling and the Transcriptional Regulator NCOR2.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 51 Downloadable Samples
- Illumina HumanHT-12 V3.0 expression beadchip
Description
Whole transcriptome profiling (Illumina Microarray) of human ex vivo lymphocytes and monocytes, as well as of human monocyte-derived cells generated in vitro by activating CD14+ monocytes with MCSF, GMCSF or the combination of GMCSF and IL4
Publication Title
Cellular Differentiation of Human Monocytes Is Regulated by Time-Dependent Interleukin-4 Signaling and the Transcriptional Regulator NCOR2.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 20 Downloadable Samples
- Illumina HiSeq 1500
Description
Whole transcriptome profiling (RNA-Seq) of a time kinetics experiment containing human monocyte-derived cells, which were activated with IL4 either directly at the start of the culture, or at different hours after an initial activation with GMCSF alone. Cells being activated solely with GMCSF were added as controls Overall design: CD14+ monocytes were FACS-sorted from blood of human healthy donors and later activated in vitro with either GMCSF alone for 72 hours to obtain Mo-GMCSF[IL4 (0h)] cells as controls, with the combination of GMCSF and IL4 for 72 hours or 144 hours to obtain Mo-GMCSF[IL4 (0-72h)] or Mo-GMCSF[IL4 (0-144h)] cells, respectively, or with first GMCSF and then with the combination of GMCSF and IL4 for different durations. For the latter, monocytes were first activated with GMCSF for either 12, 24, 48 or 72 hours, and then with GMCSF plus IL4 until a total activation time of 144 hours. This resulted in Mo-GMCSF[IL4 (12-144h)], Mo-GMCSF[IL4 (24-144h)] , Mo-GMCSF[IL4 (48-144h)] and Mo-GMCSF[IL4 (72-144h)] cells, respectively.
Publication Title
Cellular Differentiation of Human Monocytes Is Regulated by Time-Dependent Interleukin-4 Signaling and the Transcriptional Regulator NCOR2.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 1500
Description
Whole transcriptome profiling (RNA-Seq) was performed on human Mo-GMCSF[IL4 (0-72h)] cells with either NCOR2 being knocked down or corresponding WT cells Overall design: CD14+ monocytes were FACS-sorted from blood of human healthy donors and later activated in vitro with the combination of GMCSF and IL4 for 72h to obtain Mo-GMCSF[IL4 (0-72h)] cells. During the last 24 hours of activation, either siRNAs targeting NCOR2 or scrambled RNAs were added to obtain NCOR2 knock down cells and corresponding WT cells, respectively
Publication Title
Cellular Differentiation of Human Monocytes Is Regulated by Time-Dependent Interleukin-4 Signaling and the Transcriptional Regulator NCOR2.
Sample Metadata Fields
Specimen part, Subject
View Samples- Homo sapiens
- 2 Downloadable Samples
- Illumina HiSeq 4000
Description
How spatial chromosome organization influences genome integrity is still poorly understood. Here we show that DNA double-strand breaks (DSBs) mediated by topoisomerase 2 (TOP2) activities, are enriched at chromatin loop anchors with high transcriptional activity. Recurrent DSBs occur at CTCF/cohesin bound sites at the bases of chromatin loops and their frequency positively correlates with transcriptional output and directionality. The physiological relevance of this preferential positioning is indicated by the finding that genes recurrently translocating to drive leukemias, are highly transcribed and are enriched at loop anchors. These genes accumulate DSBs at recurrent hot spots that give rise to chromosomal fusions relying on the activity of both TOP2 isoforms and on transcriptional elongation. We propose that transcription and 3D chromosome folding jointly pose a threat to genomic stability, and are key contributors to the occurrence of genome rearrangements that drive cancer. Overall design: Nuclear RNA profiling in lymphoblastoid TK6 cell line
Publication Title
Spatial Chromosome Folding and Active Transcription Drive DNA Fragility and Formation of Oncogenic MLL Translocations.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 25 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The many steps involved in the production of a mature mammalian mRNA are extensively coupled, and levels of both precursors and products can be measured using expression and genomic tiling microarrays. Different probes in these arrays targeting the same transcript often give different signals; then, precursor (nascent) RNA which is present transiently at low concentrations is difficult to detect.
Publication Title
A wave of nascent transcription on activated human genes.
Sample Metadata Fields
No sample metadata fields
View Samples