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GSE20264
Homo sapiens
7 Downloadable Samples
Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Background: Previous work has identified CD11c+CD1c- dendritic cells (DCs) as the major inflammatory dermal DC population in psoriasis vulgaris and CD1c+ DCs as the resident cutaneous DC population. Objective: To further define molecular differences between these two myeloid dermal DC populations. Methods: Inflammatory and resident DCs were single-cell sorted from psoriasis lesional skin biopsies, and gene array expression profiling was performed. Results were confirmed with RT-PCR, flow cytometry, immunohistochemistry, and double label immunofluorescence. Pooled human keratinocytes were cultured for functional studies. Results: TNF-related apoptosis-inducing ligand (TRAIL), Toll-like receptors (TLRs) 1 and 2, S100A12/EN-RAGE, CD32, and many other inflammatory products were selectively expressed in inflammatory DCs than in resident DCs. Flow cytometry and immunofluorescence confirmed higher protein expression on CD1c- versus CD1c+ DCs. TRAIL receptor, death receptor 4 (DR4), was expressed on basal keratinocytes and blood vessels, and in vitro culture of keratinocytes with rh-TRAIL induced CCL20 leukocyte chemokine. Conclusion: CD11c+CD1c- inflammatory DCs in psoriatic lesional skin express a wide range of inflammatory molecules compared to skin resident CD1c+ DCs. Some molecules made by inflammatory DCs, including TRAIL, could have direct effects on keratinocytes or other skin cell types to promote disease pathogenesis.
Publication Title
Identification of TNF-related apoptosis-inducing ligand and other molecules that distinguish inflammatory from resident dendritic cells in patients with psoriasis.
Sample Metadata Fields
Subject
View Samples- Homo sapiens
- 14 Downloadable Samples
- Affymetrix Human Genome U133A 2.0 Array (hgu133a2)
Description
Our group recently described a population of antigen presenting cells that appear to be critical in psoriasis pathogenesis, termed inflammatory myeloid dendritic cells (CD11c+ BDCA1-). Triggering receptor expressed on myeloid cells type-1 (TREM-1) signaling was a major canonical pathway in the published transcriptome of these cells. TREM-1 is a member of the immunoglobulin superfamily, active through the DAP12 signaling pathway, with an unknown ligand. Activation through TREM-1 induces inflammatory cytokines including IL-8, MCP/CCL2 and TNF. We now show that TREM-1 was expressed in the skin of healthy and psoriatic patients, and there was increased soluble TREM-1 in the circulation of psoriasis patients. In psoriasis lesions, TREM-1 was co-localized with dendritic cells as well as CD31+ endothelial cells. TREM-1 expression was reduced with successful NB-UVB, etanercept and anti-IL-17 treatments. An in vitro model of PGN-activated monocytes as inflammatory myeloid DCs was developed to study TREM-1 blockade, and treatment with a TREM-1 blocking chimera decreased allogeneic Th17 activation, as well as IL-17 production. Furthermore, TREM-1 blockade of ex vivo psoriatic dendritic cells in an alloMLR also showed a decrease in IL-17. Together, these data suggest that the TREM-1 signaling pathway offers a novel therapeutic target to prevent the effects of inflammatory myeloid DCs in psoriasis.
Publication Title
TREM-1 as a potential therapeutic target in psoriasis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
Illumina HiSeq 2500
Description
Goals of the study was to compare transcripional and phenotypic response of mouse intestinal organoid cultures to the PIK3CA(H1047R) and CTNNB1(stab) oncogenes. Overall design: Two biological replicates of organoids with transgenic tdTomato-Luciferase, tdTomato-PIK3CAH1047R, tdTomato-CTNNB1stab or td-Tomato-PIK3CAH1047R-CTNNB1stab were analysed by RNA-Seq By comparing 7-10 x 10E7 50bp paired end reads per library we identify transcriptional alterations in the intestinal epithelium following expression of each or both oncogenes,
Publication Title
Oncogenic β-catenin and PIK3CA instruct network states and cancer phenotypes in intestinal organoids.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Acetate, propionate and butyrate are the main short-chain fatty acids (SCFAs) that arise from the fermentation of fibers by the colonic microbiota. While many studies focus on the regulatory role of SCFAs, their quantitative role as a catabolic or anabolic substrate for the host has received relatively little attention. To investigate this aspect, we infused conscious mice with physiological quantities of stable isotopes [1-13C]acetate, [2-13C]propionate or [2,4-13C2]butyrate directly into the cecum, which is the natural production site in mice, and analyzed their interconversion by the microbiota as well as their metabolism by the host. Cecal interconversion - pointing to microbial cross-feeding - was high between acetate and butyrate, low between butyrate and propionate and almost absent between acetate and propionate. As much as 62% of infused propionate was used in whole-body glucose production, in line with its role as gluconeogenic substrate. Conversely, glucose synthesis from propionate accounted for 69% of total glucose production. The synthesis of palmitate and cholesterol in the liver was high from cecal acetate (2.8% and 0.7%, respectively) and butyrate (2.7% and 0.9%, respectively) as substrates, but low or absent from propionate (0.6% and 0.0%, respectively). Label incorporation due to chain elongation of stearate was approximately 8-fold higher than de novo synthesis of stearate. Microarray data suggested that SCFAs exert only a mild regulatory effect on the expression of genes involved in hepatic metabolic pathways during the 6h infusion period. Altogether, gut-derived acetate, propionate and butyrate play important roles as substrates for glucose, cholesterol and lipid metabolism.
Publication Title
Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids.
Sample Metadata Fields
Sex, Specimen part, Treatment
View Samples- Drosophila melanogaster
- 2 Downloadable Samples
- Affymetrix Drosophila Genome 2.0 Array (drosophila2)
Description
Transcriptional silencing of terminal differentiation genes by the Polycomb group (PcG) machinery is emerging as a key feature of precursor cells in stem cell lineages. How, then, is this epigenetic silencing reversed for proper cellular differentiation? Here we investigate how the developmental program reverses local PcG action to allow expression of terminal differentiation genes in the Drosophila male germline stem cell lineage. We find that the silenced state, set up in precursor cells, is relieved through developmentally regulated sequential events at promoters once cells commit to spermatocyte differentiation. The programmed events include global down-regulation of PRC2, recruitment of hypophosphorylated RNA Polymerase II (Pol II) to promoters, as well as expression and action of cell-type specific homologs of subunits of TFIID (tTAFs). In addition, action of tMAC, a tissue specific version of the MIP/dREAM complex, is required both for recruitment of tTAFs to target differentiation genes and for proper cell-type specific localization of PRC1 components and tTAFs to the spermatocyte nucleolus. Together, action of the tMAC and tTAF cell-type specific chromatin and transcription machinery leads to loss of
Publication Title
Sequential changes at differentiation gene promoters as they become active in a stem cell lineage.
Sample Metadata Fields
Time
View Samples- Homo sapiens
- 7 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Seborrheic keratosis is benign cutaneous neoplasm, the etiology of which is not well-known. To characterize differential gene expression profiles in seborrheic keratosis, we investigated the genome-wide patterns of gene expression from skin with seborrhic keratosis and uninvolved normal skin using cDNA microarrays.
Publication Title
Microarray analysis reveals increased expression of ΔNp63α in seborrhoeic keratosis.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Sensitive skin is a hyperactive skin condtion, characterized by prickling, burning, itching, stinging, pain, or tingling sensation, which develops in response to various internal and external stimulants that can be tolerated by most people. The pathophysiology involved in the development of sensitive skin remains largely elusive. To characterize differential gene expression profiles in sensitive skin, we investigated the genome-wide patterns of gene expression from skin samples from subjects with sensitive or non-sensitive skin, following lactic acid challenge or normal saline application using cDNA microarrays.
Publication Title
Decreased ATP synthesis and lower pH may lead to abnormal muscle contraction and skin sensitivity in human skin.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
The causative role of activated Hedgehog signaling in liver fibrosis was investigated in vivo.
Publication Title
Hepatic expression of Sonic Hedgehog induces liver fibrosis and promotes hepatocarcinogenesis in a transgenic mouse model.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 33 Downloadable Samples
Illumina HumanWG-6 v3.0 expression beadchip, Sentrix Human-6 v2 Expression BeadChip
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Assessment and diagnostic relevance of novel serum biomarkers for early decision of ST-elevation myocardial infarction.
Sample Metadata Fields
Specimen part, Disease, Disease stage, Subject
View Samples- Homo sapiens
- 33 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip, Sentrix Human-6 v2 Expression BeadChip
Description
We aim to determine blood transcriptome-based molecular signature of acute coronary syndrome (ACS), and to identify novel serum biomarkers for early stage ST-segment-elevation myocardial infarction (STEMI)
Publication Title
Assessment and diagnostic relevance of novel serum biomarkers for early decision of ST-elevation myocardial infarction.
Sample Metadata Fields
Disease
View Samples