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GSE35378
Mus musculus
12 Downloadable Samples
Affymetrix Murine Genome U74A Version 2 Array (mgu74av2)
Description
The goal of this study is to determine the effects of adipose-specific Glut4 overexpression or knockout on changes in adipose tissue global gene expression
Publication Title
A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism.
Sample Metadata Fields
Sex, Age
View Samples- Mus musculus
- 14 Downloadable Samples
Illumina HiSeq 2500
Description
Roux-en-Y gastric bypass (RYGB) is highly effective in reversing obesity and associated diabetes. Recent observations in humans suggest a contributing role of increased circulating bile acids in mediating such effects. Here we use a diet-induced obesity mouse model and compared metabolic remission when bile flow was diverted through a gallbladder anastomosis to jejunum, ileum or duodenum (sham control). We found that only bile diversion to the ileum results in physiologic changes similar to RYGB including sustained improvements in weight, glucose tolerance and hepatic steatosis despite differential effects on hepatic gene expression. Circulating free fatty acids and triglycerides decrease while bile acids increase, particularly conjugated tauro-b-muricholic acid, an FXR antagonist. Activity of the hepatic FXR/FGF15 axis was reduced and associated with altered gut microbiota. Thus bile diversion, independent of surgical rearrangement of the gastrointestinal tract, imparts significant weight loss accompanied by improved glucose and lipid homeostasis that are hallmarks of RYGB. Overall design: Total RNA from n = 5 DIO, n = 4 GB-IL, n = 5 RYGB mice livers was extracted of total RNA and submitted fro RNAseq
Publication Title
Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
We studied whether the accumulation of lipids in the fasted kidney are derived from lipoproteins or (non-esterified fatty acids) NEFAs. With overnight fasting, kidneys accumulated triglyceride, but had reduced levels of ceramide and glycosphingolipid species. Fasting led to a nearly 5-fold increase in kidney uptake of plasma [14C]oleic acid. Increasing circulating NEFAs using a ß adrenergic receptor agonist caused a 15-fold greater accumulation of lipid in the kidney, while mice with reduced NEFAs due to adipose tissue deficiency of adipose triglyceride lipase had reduced triglycerides. Cluster of differentiation (Cd)36 mRNA increased 2-fold, and angiopoietin-like 4 (Angptl4), an LPL inhibitor, increased 10-fold. Fasting-induced kidney lipid accumulation was not affected by inhibition of LPL with poloxamer 407 or by use of mice with induced genetic LPL deletion. Despite the increase in CD36 expression with fasting, genetic loss of CD36 did not alter fatty acid uptake or triglyceride accumulation. Our data demonstrate that fasting-induced triglyceride accumulation in the kidney correlates with the plasma concentrations of NEFAs, but is not due to uptake of lipoprotein lipids and does not involve the fatty acid transporter, CD36. Overall design: Mice (n=4-5/group) were either fasted for 16 hours or fed ad libitum. Kidneys were removed and snap frozen. RNA was extracted for sequencing.
Publication Title
Kidney triglyceride accumulation in the fasted mouse is dependent upon serum free fatty acids.
Sample Metadata Fields
Sex, Cell line, Treatment, Subject
View Samples- Mus musculus
- 8 Downloadable Samples
- Illumina HiSeq 2500
Description
Macrophages polarize to divergent functional phenotypes depending on their microenvironment in a highly coordinated process of metabolic and transcriptional rewiring that is still poorly understood. We developed an Integrated Metabolomics and Gene Expression (IMAGE) profiling and analysis pipeline and applied it to extensively characterize global metabolic programs of macrophage polarization. IMAGE analysis identified 7 major (novel and known) regulatory modules responsible for metabolic rewiring during polarization, which we validated through extensive carbon and nitrogen labeling experiments. M1-specific modules included: inflammatory variant of the aspartate-arginosuccinate shunt; TCA cycle break at Idh expression accompanied by citrate accumulation and production of itaconate and fatty acid synthesis. In M2 macrophages we discovered significant role of glutamine in polarization, providing nitrogen for UDP-GlcNAc synthesis. Consistently, glutamine deprivation results in significant M2-specific defect in polarization. Our data provide, for the first time, a global view of the integrated transcriptional and metabolic changes that result in M1 and M2 polarization. Overall design: Bone-marrow derived macrophages were generated from C57BL/6 mice were plated at ~100k cells per well in 96-well plate and stimulated with either Il4 or combination of LPS&IFNg or left unstimulated for 24 h mRNA was derived from lysates using Invitrogen oligo-dT beads
Publication Title
Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 31 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Despite numerous observations of effects of estrogens on spermatogenesis, identification of estrogen-regulated genes in the testis is limited. We previously showed in rats, in which irradiation had completely blocked spermatogonial differentiation, that testosterone (T) suppression with GnRH-antagonist and antiandrogen stimulated spermatogenic recovery and addition of estradiol (E2) to this regimen accelerated this recovery. We report here the global changes in testicular cell gene expression induced by the E2 treatment. By minimizing the changes in other hormones and also having concurrent data on the regulation of the genes by those hormones, we were able to dissect the effects of estrogen on gene expression, independent of gonadotropin or T changes. Expression of 20 genes, largely in somatic cells, was up- or down-regulated between 2- and 5-fold by E2. There were also early germ cell genes whose expression increased but this was a result of a small increase in spermatogonial numbers. The striking enrichment of transcripts not corresponding to known genes among the E2-downregulated probes led to the identification of one as micro-RNA miR-34a. We propose that genes whose expression levels are altered in one direction by irradiation and in the opposite direction by both T suppression and E2 treatment are candidates for controlling the block in differentiation. Several genes, including insulin-like 3 (Insl3), satisfied those criteria. If they are indeed involved in the inhibition of spermatogonial differentiation, they may be candidate targets for clinical treatments to enhance recovery of spermatogenesis following gonadotoxic exposures, such as those resulting from cancer therapy.
Publication Title
Estrogen-regulated genes in rat testes and their relationship to recovery of spermatogenesis after irradiation.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 12 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Analysis of the human monocyte-derived macrophage (hMDM) transcriptional response to L. pneumophila infection at 8 hours post-infection
Publication Title
The transcriptome of Legionella pneumophila-infected human monocyte-derived macrophages.
Sample Metadata Fields
Specimen part
View Samples- Bos taurus
- 24 Downloadable Samples
- Bovine Gene 1.1 ST Array (bovgene11st)
Description
Infection with non-cytopathic bovine viral diarrhea virus (ncpBVDV) is associated with uterine disease and infertility. This study investigated the influence of ncpBVDV on immune functions of the bovine endometrium by testing the response to bacterial lipopolysaccharide (LPS) at the level of whole-transcriptomic gene expression. Analysis showed that approximately 30% of the 1,006 genes altered by LPS are involved in immune response. Many innate immune genes that typically respond to LPS were inhibited by ncpBVDV including those involved in pathogen recognition, inflammation, interferon response, chemokines, tissue remodeling, cell migration and cell death/survival. Infection with ncpBVDV can thus compromise immune function and pregnancy recognition thereby potentially predisposing infected cows to postpartum bacterial endometritis and reduced fertility.
Publication Title
Global transcriptomic profiling of bovine endometrial immune response in vitro. I. Effect of lipopolysaccharide on innate immunity.
Sample Metadata Fields
Sex, Treatment
View Samples- Homo sapiens
- 15 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Intercellular communication is critical for integrating complex signals in multicellular eukaryotes. Vascular endothelial cells and T lymphocytes closely interact during the recirculation and trans-endothelial migration of T cells. In addition to direct cell-cell contact, we show that T cell derived extracellular vesicles can interact with endothelial cells and modulate their cellular functions. Thrombospondin-1 and its receptor CD47 are expressed on exosomes/ectosomes derived from T cells, and these extracellular vesicles are internalized and modulate signaling in both T cells and endothelial cells. Extracellular vesicles released from cells expressing or lacking CD47 differentially regulate activation of T cells induced by engaging the T cell receptor. Similarly, T cell-derived extracellular vesicles modulate endothelial cell responses to vascular endothelial growth factor and tube formation in a CD47-dependent manner. Uptake of T cell derived extracellular vesicles by recipient endothelial cells globally alters gene expression in a CD47-dependent manner. CD47 also regulates the mRNA content of extracellular vesicles in a manner consistent with some of the resulting alterations in target endothelial cell gene expression. Therefore, the thrombospondin-1 receptor CD47 directly or indirectly regulates intercellular communication mediated by the transfer of extracellular vesicles between vascular cells.
Publication Title
CD47-dependent immunomodulatory and angiogenic activities of extracellular vesicles produced by T cells.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Homo sapiens
- 36 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
We performed expression profiling of 36 types of normal human tissues and identified 2,503 tissue-specific genes. We then systematically studied the expression of these genes in cancers by re-analyzing a large collection of published DNA microarray datasets. Our study shows that integration of each gene's breadth of expression (BOE) in normal tissues is important for biological interpretation of the expression profiles of cancers in terms of tumor differentiation, cell lineage and metastasis.
Publication Title
Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues.
Sample Metadata Fields
No sample metadata fields
View Samples- Rattus norvegicus
- 16 Downloadable Samples
- Affymetrix Rat Genome 230 2.0 Array (rat2302)
Description
Nutritional status influences feeding behaviors, food preferences and taste sensations. For example, zinc-deficient rats have been reported to show reduced and cyclic food intake patterns with increased preferences for NaCl. Although some impairments of the central nervous and endocrine systems have been speculated to be involved in these phenomena, the effects of short-term zinc deficiency on the brain have not been well examined to date. In this study, we performed a comprehensive analysis of the gene expression patterns in the rat diencephalon, which is a portion of the brain that includes the hypothalamus and thalamus, after short-term zinc deficiency and also during zinc recovery. The rats showed reduced and cyclic food intake patterns with increased salt preferences after a 10-day dietary zinc deficiency. A comparative analysis of their diencephalons using cDNA microarrays revealed that approximately 1% of the genes expressed in the diencephalons showed significantly altered expression levels. On the other hand, a 6-day zinc supplementation following the deprivation allowed for the recovery to initial food intake behaviors and salt preferences. The expression levels of most of the genes that had been altered by exposure to zinc deficient conditions were also recovered. These results show that feeding behaviors, taste preferences and gene expression patterns in the diencephalon respond quickly to changing zinc levels. This suggests that the gene expression changes observed in the diencephalon and the accompanying functional changes may be related to the development of deviations in feeding behaviors and increased preferences for NaCl in zinc-deficient rats.
Publication Title
Dietary zinc status reversibly alters both the feeding behaviors of the rats and gene expression patterns in diencephalon.
Sample Metadata Fields
Sex, Treatment
View Samples