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E-MEXP-88
Drosophila melanogaster
8 Downloadable Samples
Affymetrix Drosophila Genome Array (drosgenome1)
Description
THO2 and HPR1 proteins were co-depleted from Drosophila S2 cells and their role in mRNA export analysed by comparing total RNA and cytoplasmic RNA
Publication Title
The superhelical TPR-repeat domain of O-linked GlcNAc transferase exhibits structural similarities to importin alpha.
Sample Metadata Fields
Cell line
View Samples- Rattus norvegicus
- 11 Downloadable Samples
Illumina Genome Analyzer IIx
Description
Maternal obesity can program metabolic syndrome in offspring but the mechanisms are not well characterized. Moreover, the consequences of maternal overnutrition in the absence of frank obesity remain poorly understood. This study aimed to determine the effects of maternal consumption of a high fat-sucrose diet on the skeletal muscle metabolic and transcriptional profiles of adult offspring. Female Sprague Dawley rats were fed either a diet rich in saturated fat and sucrose (HFD, 23.5% fat, 20% sucrose wt/wt) or a standard chow diet (NFD, 7% fat, 10% sucrose w/w) for the 3 weeks prior to mating and throughout pregnancy and lactation. Although maternal weights were not different between groups at conception or weaning, HFD dams were ~22% heavier than chow fed dams from mid-pregnancy until 4 days post-partum. Adult male offspring of HFD dams were not heavier than controls but demonstrated features of insulin resistance including elevated plasma insulin concentration (+40%, P<0.05). Next Generation mRNA Sequencing was used to identify differentially expressed genes in the soleus muscle of offspring, and Gene Set Enrichment Analysis (GSEA) to detect coordinated changes that are characteristic of a biological function. GSEA identified 15 pathways enriched for up-regulated genes, including cytokine signaling (P<0.005), starch and sucrose metabolism (P<0.017), and inflammatory response (P<0.024). A further 8 pathways were significantly enriched for down-regulated genes including oxidative phosphorylation (P<0.004) and electron transport (P<0.022). Western blots confirmed a ~60% reduction in the phosphorylation of the insulin signaling protein Akt (P<0.05) and ~70% reduction in mitochondrial complexes II (P<0.05) and V expression (P<0.05). On a normal diet, offspring of HFD dams developed an insulin resistant phenotype, with transcriptional evidence of muscle cytokine activation, inflammation and mitochondrial dysfunction. These data indicate that maternal overnutrition, even in the absence of pre-pregnancy obesity can promote metabolic dysregulation and predispose offspring to type 2 diabetes. Overall design: Messenger RNA profile of skeletal muscle of male offspring from female Sprague Dawley rats fed either a diet rich in saturated fat and sucrose (HFD, 23.5% fat, 20% sucrose wt/wt) or a standard chow diet (NFD, 7% fat, 10% sucrose w/w) for the 3 weeks prior to mating and throughout pregnancy and lactation. There were 5 HFD samples compared to 6 NFD control samples.
Publication Title
Maternal overnutrition programs changes in the expression of skeletal muscle genes that are associated with insulin resistance and defects of oxidative phosphorylation in adult male rat offspring.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 40 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Temporal changes of gene expression from 1-wk- to 4-wk and 8-wk-old mouse in heart, kidney and lung. Mammalian somatic growth is rapid in early postnatal life but then slows and eventually ceases in multiple tissues. We hypothesized that there exists a postnatal gene expression program that is common to multiple tissues and is responsible for this coordinate growth deceleration. Consistent with this hypothesis, microarray analysis identified >1600 genes that were regulated with age coordinately in kidney, lung, and heart of juvenile mice, including many genes that regulate proliferation. As examples, we focused on three growth-promoting genes, Igf2, Mest, and Peg3, that were markedly downregulated with age. We conclude that there exists an extensive genetic program occurring during postnatal life. Many of the involved genes are regulated coordinately in multiple organs, including many genes that regulate cell proliferation. At least some of these are themselves apparently regulated by growth, suggesting that, in the embryo, a gene expression pattern is established that allows for rapid somatic growth of multiple tissues but then, during postnatal life, this growth leads to negative-feedback changes in gene expression that in turn slow and eventually halt somatic growth, thus imposing a fundamental limit on adult body size.
Publication Title
An extensive genetic program occurring during postnatal growth in multiple tissues.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
How organ size and form are controlled during development is a major question of biology. Blood vessels have been shown to be essential for early development of the liver and pancreas, and are fundamental to normal and pathological tissue growth. Here we report that non-nutritional signals from blood vessels surprisingly act to restrain pancreas growth. Elimination of endothelial cells increases the size of embryonic pancreatic buds. Conversely, VEGF-induced hypervascularization decreases pancreas size. The growth phenotype results from vascular restriction of pancreatic tip cell formation, lateral branching and differentiation of the pancreatic epithelium into endocrine and acinar cells. The effects are seen both in vivo and ex vivo, indicating a perfusion-independent mechanism. Thus the vasculature controls pancreas morphogenesis and growth by reducing branching and differentiation of primitive epithelial cells.
Publication Title
Blood vessels restrain pancreas branching, differentiation and growth.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Rosiglitazone (Rosi), a member of the thiazolidinedione class of drugs used to treat type 2 diabetes, activates the adipocyte-specific transcription factor peroxisome proliferator-activated receptor gamma (PPARg). This activation causes bone loss in animals and humans, at least in part due to suppression of osteoblast differentiation from marrow mesenchymal stem cells (MSC). In order to identify mechanisms by which PPARg2 suppresses osteoblastogenesis and promotes adipogenesis in MSC, we have analyzed the PPARg2 transcriptome in response to Rosi. A total of 4,252 transcriptional changes resulted when Rosi (1 uM) was applied to the U-33 marrow stromal cell line, stably transfected with PPARg2 (U-33/g2), as compared to non-induced U-33/g2 cells. Differences between U-33/g2 and U-33 cells stably transfected with empty vector (U-33/c) comprised 7,928 transcriptional changes, independent of Rosi. Cell type-, time- and treatment-specific gene clustering uncovered distinct patterns of PPARg2 transcriptional control of MSC lineage commitment. The earliest changes accompanying Rosi activation of PPARg2 included adjustments in morphogenesis, Wnt signaling, and immune responses, as well as sustained induction of lipid metabolism. Expression signatures influenced by longer exposure to Rosi provided evidence for distinct mechanisms governing the repression of osteogenesis and stimulation of adipogenesis. Our results suggest interactions that could lead to the identification of a master regulatory scheme controlling osteoblast differentiation.
Publication Title
PPARgamma2 nuclear receptor controls multiple regulatory pathways of osteoblast differentiation from marrow mesenchymal stem cells.
Sample Metadata Fields
Compound, Time
View Samples- Rattus norvegicus
- 12 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Appropriate nutrition during early development is essential for optimal bone mass accretion; however, linkage between early nutrition, childhood bone mass and prevention of bone loss later in life has not been extensively studied. In this report, we have demonstrated several fundamental issues in the field. 1) A significant prevention of ovariectomy (OVX) -induced bone loss from adult rats can occur with only 14 days consumption of a blueberry-containing diet immediately prior to puberty. 2) The molecular mechanisms underlying these effects involve increased myosin production and preserved a shuttle for transcription factors such as Runx2 from cytoplasm to nucleolus which stimulates osteoblast differentiation and reduces mesenchymal stromal cell senescence. 3) The effects of blueberry diet on preserving fidelity of osteoblast differentiation also overcome reduced osteoblast differentiation and activity due to OVX-induced degradation of collagen matrix.
Publication Title
Feeding blueberry diets in early life prevent senescence of osteoblasts and bone loss in ovariectomized adult female rats.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
Blockades in hematopoiesis deprive the host of vital blood cells and frequently cause leukemia. Here we show that inactivation of mTORC1 in hematopoietic stem cells by deletion of Raptor unmasked a cell type, hereby called myelolymphoblastic innate cell (MLIC) based on unique gene expression signature, cell surface markers, morphology and functions. The MLICs are CD11b(+)Gr-1(-)B7-H1(high)F4/80(low) and have morphology of lymphoblasts with active Ig loci but no gene rearrangement. Within weeks of Raptor deletion, the MLICs account for nearly 50% of bone marrow cells and are found throughout both the lymphoid and non-lymphoid organs. Nevertheless, the MLICs are not malignant as they undergo very limited proliferation in vivo. Importantly, the MLICs broadly express pattern-recognition receptors and produce large amounts of inflammatory cytokines in response to all TLR ligands tested, rendering the host highly susceptible to pathogen-associated molecular patterns. Our data suggest that hematopoietic cell-intrinsic mTORC1 prevents development of self-destructive innate immune attack by suppressing generation of MLICs. Overall design: Raptor F/F mice were crossed with Mx1-Cre mice for more than 2 generations to get Raptor F/F (Ctrl) and Raptor F/F, Mx1-Cre (cKO) mice. Sex-matched 6-8 weeks old Ctrl mice and cKO mice were treated with polyinosinic: polycytidylic acid (pIpC) every other day for consecutive 7 times by intra-peritoneal (i.p.) injection to induce Cre expression and Raptor deletion in mouse hematopoietic system. Raptor mice were sacrificed 2-3 weeks after the last injection of pIpC. Whole BM cells from Raptor Ctrl mice (n=3) and FACS-sorted CD11b(+)Gr-1(-) BM MLICs from Raptor cKO mice (n=3) were used for RNA isolation and subsequent cDNA libraries construction. mRNA profiles of Ctrl-WBM and cKO-MLIC were examined by RNA-sequencing, in triplicate, using Illumina HiSeq 2000.
Publication Title
A population of innate myelolymphoblastoid effector cell expanded by inactivation of mTOR complex 1 in mice.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 200 Downloadable Samples
- Illumina humanRef-8 v2.0 expression beadchip
Description
Analysis of expression quantitative trait loci (eQTLs) using RNA derived from freshly harvested peripheral blood CD4+ lymphocytes from 200 asthmatics collected in clinical settings.
Publication Title
Mapping of numerous disease-associated expression polymorphisms in primary peripheral blood CD4+ lymphocytes.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Chronic lymphocytic leukemia (CLL) is a disorder of mature B cells. Most patients are characterized by indolent disease and an anergic phenotype of their leukemia cells which refers to a state of unresponsiveness to B cell receptor stimulation. Using the E-TCL1 mouse model, we show that B cell-specific ablation of NFAT2 leads to the loss of the anergic phenotype culminating in a significantly compromised life expectancy and histological transformation to aggressive disease. We further define a gene expression signature of anergic CLL cells consisting of several NFAT2-dependant genes employing microarray technology.
Publication Title
NFAT2 is a critical regulator of the anergic phenotype in chronic lymphocytic leukaemia.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Histone deacetylase 3 (HDAC3) is an epigenome-modifying enzyme that is required for normal mouse development and tissue-specific functions. In vitro, HDAC3 protein itself has minimal enzyme activity, but gains its histone deacetylation function from stable association with the conserved deacetylase activation domain (DAD) contained in nuclear receptor corepressors NCOR1 and SMRT. Here we show that HDAC3 enzyme activity is undetectable in mice bearing point mutations in the DAD of both NCOR1 and SMRT (NS-DADm), despite normal levels of HDAC3 protein. Local histone acetylation is increased, and genomic HDAC3 recruitment is reduced though not abrogated. Remarkably, the NS-DADm mice are born and live to adulthood, whereas genetic deletion of HDAC3 is embryonic lethal. These findings demonstrate that nuclear receptor corepressors are required for HDAC3 enzyme activity in vivo, and suggest that a deacetylase-independent function of HDAC3 may be required for life.
Publication Title
Nuclear receptor co-repressors are required for the histone-deacetylase activity of HDAC3 in vivo.
Sample Metadata Fields
Specimen part, Time
View Samples