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,
Oncogenic β-catenin and PIK3CA instruct network states and cancer phenotypes in intestinal organoids.
Specimen part, Cell line, Subject
View SamplesAcetate, 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.
Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids.
Sex, Specimen part, Treatment
View SamplesTranscriptional 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
Sequential changes at differentiation gene promoters as they become active in a stem cell lineage.
Time
View SamplesSeborrheic 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.
Microarray analysis reveals increased expression of ΔNp63α in seborrhoeic keratosis.
Specimen part
View SamplesSensitive 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.
Decreased ATP synthesis and lower pH may lead to abnormal muscle contraction and skin sensitivity in human skin.
Specimen part
View SamplesThe causative role of activated Hedgehog signaling in liver fibrosis was investigated in vivo.
Hepatic expression of Sonic Hedgehog induces liver fibrosis and promotes hepatocarcinogenesis in a transgenic mouse model.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Assessment and diagnostic relevance of novel serum biomarkers for early decision of ST-elevation myocardial infarction.
Specimen part, Disease, Disease stage, Subject
View SamplesWe 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)
Assessment and diagnostic relevance of novel serum biomarkers for early decision of ST-elevation myocardial infarction.
Disease
View SamplesBackground: 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.
Identification of TNF-related apoptosis-inducing ligand and other molecules that distinguish inflammatory from resident dendritic cells in patients with psoriasis.
Subject
View SamplesWe undertook an inter-laboratory effort to generate high-quality quantitative data for a very large number of cellular components in yeast using transcriptome and metabolome analysis. We ensured the high-quality of the experimental data by evaluating a wide range of sampling and measurement techniques. The data were generated for two different yeast strains, each growing under two different growth conditions and based on integrated analysis of the high-throughput data we hypothesize that differences in growth rates and yields on glucose between the two strains are due to differences in protein metabolism.
Integrated multilaboratory systems biology reveals differences in protein metabolism between two reference yeast strains.
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