We report the transcriptional changes associated with treatment of U2OS osteosarcoma cell line with DMSO, AML108, AMN107, BGW675, JAA804, LEE837 and LHD510. Overall design: U2OS cells were treated with 100nM, 1000nM and 10000nM of DMSO, AML108, AMN107, BGW675, JAA804, LEE837 and LHD510 for 12 hrs and subjected to RNA-seq.
DRUG-seq for miniaturized high-throughput transcriptome profiling in drug discovery.
Specimen part, Cell line, Treatment, Subject
View SamplesMost commonly used models of non-alcoholic steatohepatitis (NASH) are diets based on specific gene knockouts or represent extreme manipulations of diet. We have examined the effects of modest increased caloric intake and high dietary unsaturated fat content on the development of NASH in male rats using a model in which overfeeding is accomplished via intragastric infusion of liquid diets as a part of total enteral nutrition. Male Sprague dawley rats were fed diets 5% corn oil containing diets at 187 Kcal/kg3/4/d or fed 70% corn oil containing diets at 220 Kcal/kg3/4/d for a period of 3 weeks. Hepatic gene expression were assessed at the end of the study. Our results indicate that overfeeding of high unsaturated fat diets leads to pathological, endocrine and metabolic changes characteristic of NASH patients and is associated with increased oxidative stress and TNF-a.
A new model for nonalcoholic steatohepatitis in the rat utilizing total enteral nutrition to overfeed a high-polyunsaturated fat diet.
No sample metadata fields
View SamplesIntestinal health is sustained by cooperation between diverse cell types, including epithelial cells, immune cells and stromal cells. Colonic stromal cells provide critical structural support but also regulate mucosal immunity, tolerance and inflammatory responses. Although mucosal stromal cells display substantial variability and plasticity, a paucity of unique genetic markers has precluded the identification of distinct stromal populations and functions. We used single-cell RNA-sequencing to uncover heterogeneity and subtype-specific markers of individual colonic stromal cells in health and ulcerative colitis (UC). Marker-free transcriptional clustering revealed four distinct stromal populations in healthy colon, corresponding to myofibroblasts and three previously unknown distinct subsets of fibroblasts. These fibroblast subsets were substantially remodeled in UC compared to healthy colon: inflamed UC colon was depleted for a healthy fibroblast subpopulation associated with epithelial cell homeostasis, and enriched for a novel disease-associated subtype expressing pro-inflammatory genes. Thus, we have discovered new, molecularly distinct colonic stromal cell subtypes that are altered in human disease. Overall design: Colonic lamina propria mesenchymal cells from 3 healthy donors. 183 single cell libraries, 6 bulk controls, 3 empty well controls. Individual donors processed as separate batches with Fluidigm C1 IFCs and pooled for sequencing (2 x Illumina HiSeq 2500 lanes).
Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease.
No sample metadata fields
View SamplesIntestinal health is sustained by cooperation between diverse cell types, including epithelial cells, immune cells and stromal cells. Colonic stromal cells provide critical structural support but also regulate mucosal immunity, tolerance and inflammatory responses. Although mucosal stromal cells display substantial variability and plasticity, a paucity of unique genetic markers has precluded the identification of distinct stromal populations and functions. We used single-cell RNA-sequencing to uncover heterogeneity and subtype-specific markers of individual colonic stromal cells in health and ulcerative colitis (UC). Marker-free transcriptional clustering revealed four distinct stromal populations in healthy colon, corresponding to myofibroblasts and three previously unknown distinct subsets of fibroblasts. These fibroblast subsets were substantially remodeled in UC compared to healthy colon: inflamed UC colon was depleted for a healthy fibroblast subpopulation associated with epithelial cell homeostasis, and enriched for a novel disease-associated subtype expressing pro-inflammatory genes. Thus, we have discovered new, molecularly distinct colonic stromal cell subtypes that are altered in human disease. Overall design: Ulcerative colitis colonic lamina propria mesenchymal cells from 3 donors. 178 single cell libraries, 7 bulk controls, 7 empty well controls. Individual donors processed as separate batches on Fluidigm C1 IFCs and pooled for sequencing (1 x Illumina HiSeq 4000 lane).
Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease.
Disease, Subject
View SamplesIntestinal health is sustained by cooperation between diverse cell types, including epithelial cells, immune cells and stromal cells. Colonic stromal cells provide critical structural support but also regulate mucosal immunity, tolerance and inflammatory responses. Although mucosal stromal cells display substantial variability and plasticity, a paucity of unique genetic markers has precluded the identification of distinct stromal populations and functions. We used single-cell RNA-sequencing to uncover heterogeneity and subtype-specific markers of individual colonic stromal cells in health and ulcerative colitis (UC). Marker-free transcriptional clustering revealed four distinct stromal populations in healthy colon, corresponding to myofibroblasts and three previously unknown distinct subsets of fibroblasts. These fibroblast subsets were substantially remodeled in UC compared to healthy colon: inflamed UC colon was depleted for a healthy fibroblast subpopulation associated with epithelial cell homeostasis, and enriched for a novel disease-associated subtype expressing pro-inflammatory genes. Thus, we have discovered new, molecularly distinct colonic stromal cell subtypes that are altered in human disease. Overall design: Colonic epithelial cells from 3 healthy donors. 92 single cell libraries, 3 bulk controls, 1 empty well control. Individual donors processed as separate batches on Fluidigm C1 IFCs and pooled for sequencing (1 x Illumina HiSeq 2500 lane).
Structural Remodeling of the Human Colonic Mesenchyme in Inflammatory Bowel Disease.
Disease, Subject
View SamplesSoy foods have been suggested to have both positive health benefits and potentially adverse effects largely as a result of their content of isoflavone phytoestrogens. Since soy protein isolate (SPI) contains isoflavones, in addition to purported health benefits, safety concerns have been raised regarding the use of SPI and soy formulas, because of potential estrogenic actions during the neonatal period, including the potential for reproductive toxicity, infertility, and the possibility of increased risk for development and recurrence of estrogen sensitive cancers such as breast cancer. In the current study, we used a rat model to compare the effects of SPI with those of 17b-estradiol (E2), on global gene expression profiles and morphology in the female rat mammary gland. Rats were either fed AIN-93G diets containing casein (CAS) or SPI beginning on postnatal day (PND) 30.
Mammary gland morphology and gene expression differ in female rats treated with 17β-estradiol or fed soy protein isolate.
Sex
View SamplesThe current study was designed to determine if dietary fatty acid concentration and composition affects the development and progression of nonalcoholic fatty liver disease. Male SD rats were overfed diets low (5%) or high (70%) fat diets via total enteral nutrition where the fat source was olive oil (monounsaturated), or corn oil (polyunsaturated). Overfeeding 5% corn oil produced little steatosis relative to feeding 5% olive oil. This was associated with lower fatty acid synthesis and reduced SREBP-c signaling in the 5% corn oil group. Overfeeding 70% fat diets increased steatosis and lead to increased liver necrosis in the 70% corn oil but not olive oil group. Increased injury after feeding polyunsaturated fat diets was linked to peroxidizability of hepatic free fatty acids and triglycerides and appearance of peroxidaized lipid products HETES and HODES previously linked to clinical nonalcoholic steatohepatitis.
Dietary fat source alters hepatic gene expression profile and determines the type of liver pathology in rats overfed via total enteral nutrition.
Sex
View SamplesIn order to properly understand whether xenoestrogens act as estrogens, it is essential to possess a solid portrait of the physiological effects of exogenous estradiol. Because the estrogen-dependent gene expression is one of the primary biomarkers of estrogenic action, we have assessed effects of three doses of exogenous estradiol (0.1, 1.0 and 10 g/kg of body weight/day) on the mammary gland morphology and gene expression profiles by microarray analysis of prepubertal male and female rats of both sexes compared to untreated controls. Estradiol was administered subcutaneously with minipumps from weaning at PND21 to the end of the experiment at PND33. The data suggest that the male mammary is a sensitive tissue for estrogenicity assessment.
Mammary gland morphology and gene expression signature of weanling male and female rats following exposure to exogenous estradiol.
Sex
View SamplesIn order to study the transcriptional response of the fly brain to sugar and complete starvation, we first confirmed that 24 hours of sugar and complete starvation in flies is sufficient to elicit a homeostatic response. Subsequently, we used holidic medium to study effects of deficiency of a specfic macronutrient- cabohydrate in the food. To do so , we generated RNA- seq libraries from brains of 5 day old mated adult male flies maintained on different feeding regimes and used the sequencing data to identify diffrentially expressed genes in the brain under different feeding regimes. Overall design: For each condition, we used RNA prepared from 120-130 manually dissected adult fly brains maintained under complete starvation or sugar starvation regime for 24 hours.
Sugar Promotes Feeding in Flies via the Serine Protease Homolog scarface.
Sex, Specimen part, Cell line, Subject
View SamplesWhile the existence of intestinal epithelial stem cells (IESCs) has been well established, their study has been limited due to the inability to isolate them. Previous work has utilized side population (SP) sorting of the murine small intestinal mucosa to isolate a viable fraction of cells enriched for putative IESCs. We have used microarray analyses to characterize the molecular features of this potential stem cell population.
Molecular properties of side population-sorted cells from mouse small intestine.
No sample metadata fields
View Samples