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GSE21517
Xenopus laevis
9 Downloadable Samples
Affymetrix Xenopus laevis Genome Array (xenopuslaevis)
Description
ADAMs are transmembrane metalloproteases that control cell behavior by cleaving both cell adhesion and signaling molecules. The cytoplasmic domain of ADAMs can regulate the proteolytic activity by controlling the subcellular localization and/or the activation of the protease domain. Here we show that the cytoplasmic domain of ADAM13 is cleaved and translocates into the nucleus. Preventing this translocation renders the protein incapable of promoting cranial neural crest (CNC) cell migration in vivo, without affecting its proteolytic activity. In addition, the cytoplasmic domain of ADAM13 regulates the expression of multiple genes in the CNC. This study shows that the cytoplasmic domain of ADAM metalloproteases can perform essential functions in the nucleus of cells and may contribute substantially to the overall function of the protein.
Publication Title
Translocation of the cytoplasmic domain of ADAM13 to the nucleus is essential for Calpain8-a expression and cranial neural crest cell migration.
Sample Metadata Fields
Specimen part
View Samples- Caenorhabditis elegans
- 8 Downloadable Samples
- Affymetrix C. elegans Genome Array (celegans)
Description
The PUF family of RNA binding proteins has a conserved role in maintaining stem cell self-renewal. FBF is a C. elegans PUF that is required to maintain germline stem cells (GSCs). To understand how FBF controls GSCs, we sought to identify is target mRNAs. Briefly, we immunoprecipitated FBF-mRNA complexes from worm extracts and then used microarrays to identify the FBF-associated mRNAs. To focus on germline targets of FBF, we used a FBF-GFP transgene under the control of a germline promoter and we used an anti-GFP antibody to purify FBF-GFP from worm extracts. In parallel, we also processed a strain expressing TUBULIN-GFP in the germline to control for mRNAs that non-specifically co-purify with GFP. We found that FBF associates with >1,000 unique mRNAs and likely controls a broad network of key cellular and developmental regulators.
Publication Title
Genome-wide analysis of mRNA targets for Caenorhabditis elegans FBF, a conserved stem cell regulator.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.1 ST Array (mogene11st)
Description
Inflammasome activation in adipose tissue has been implicated in obesity-associated insulin resistance and type 2 diabetes. However, when and how inflammasome is activated in adipose tissue remains speculative. Here we test the hypothesis that extracellular ATP, a potent stimulus of inflammasome in macrophages via purinergic receptor P2X, ligand-gated ion channel, 7 (P2X7), may play a role in inflammasome activation in adipose tissue in obesity. Our data show that inflammasome is activated in adipose tissue upon 8-week feeding of 60% HFD, coinciding with the onset of hyperglycemia and hyperinsulinemia as well as the induction of P2X7 in adipose tissue. Unexpectedly, P2X7-deficient animals on HFD exhibit no changes in metabolic phenotypes, nor in inflammatory responses or inflammasome activation when compared to the wildtype controls. Similar observations have been obtained in hematopoietic cell-specific P2X7-deficient animals generated by bone marrow transplantation. Thus, we conclude that inflammasome activation in adipose tissue in obesity coincides with the onset of hyperglycemia and hyperinsulinemia, but unexpectedly, is not mediated by the ATP-P2X7 signaling axis. The nature of the inflammasome-activating danger signal(s) in adipose tissue in obesity remains to be characterized.
Publication Title
The ATP-P2X7 signaling axis is dispensable for obesity-associated inflammasome activation in adipose tissue.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 55 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Detailed transcriptomics analysis of the effect of dietary fatty acids on gene expression in the heart.
Sample Metadata Fields
Sex, Treatment
View Samples- Mus musculus
- 55 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Fatty acids comprise the primary energy source for the heart and are mainly taken up via hydrolysis of circulating triglyceride-rich lipoproteins. While most of the fatty acids entering the cardiomyocyte are oxidized, a small portion is involved in altering gene transcription to modulate cardiometabolic functions. So far, no in vivo model has been developed enabling study of the transcriptional effects of specific fatty acids in the intact heart. In the present study, mice were given a single oral dose of synthetic triglycerides composed of one single fatty acid. Hearts were collected 6h thereafter and used for whole genome gene expression profiling. Experiments were conducted in wild-type and PPAR/ mice to allow exploration of the specific contribution of PPAR. It was found that: 1) linolenic acid (C18:3) had the most pronounced effect on cardiac gene expression. 2) The largest similarity in gene regulation was observed between linoleic acid (C18:2) and C18:3. Large similarity was also observed between the synthetic PPAR agonist Wy14643 and docosahexaenoic acid (C22:6). 3) Many genes were regulated by one particular treatment only. Genes regulated by one particular treatment showed large functional divergence. 4) The majority of genes responding to fatty acid treatment were regulated in a PPAR-dependent manner, emphasizing the importance of PPAR in mediating transcriptional regulation by fatty acids in the heart. 5) Several genes were robustly regulated by all or many of the fatty acids studied, mostly representing well-described targets of PPARs (e.g. Acot1, Angptl4, Ucp3). 6) Deletion and activation of PPAR had a major effect on expression of numerous genes involved in metabolism and immunity. Our analysis demonstrates the marked impact of dietary fatty acids on gene regulation in the heart via PPAR.
Publication Title
Detailed transcriptomics analysis of the effect of dietary fatty acids on gene expression in the heart.
Sample Metadata Fields
Sex, Treatment
View Samples- Mus musculus, Homo sapiens
- 46 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Studies in mice have shown that PPAR is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPAR in human liver. Here we set out to compare the function of PPAR in mouse and human hepatocytes via analysis of target gene regulation. Primary hepatocytes from 6 human and 6 mouse donors were treated with PPAR agonist Wy14643 and gene expression profiling was performed using Affymetrix GeneChips followed by a systems biology analysis. Baseline PPAR expression was similar in human and mouse hepatocytes. Depending on species and time of exposure, Wy14643 significantly induced the expression of 362-672 genes. Surprisingly minor overlap was observed between the Wy14643-regulated genes from mouse and human, although more substantial overlap was observed at the pathway level. Xenobiotics metabolism and apolipoprotein synthesis were specifically regulated by PPAR in human hepatocytes, whereas glycolysis-gluconeogenesis was regulated specifically in mouse hepatocytes. Most of the genes commonly regulated in mouse and human were involved in lipid metabolism and many represented known PPAR targets, including CPT1A, HMGCS2, FABP, ACSL, and ADFP. Several genes were identified that were specifically induced by PPAR in human (MBL2, ALAS1, CYP1A1, TSKU) or mouse (Fbp2, lgals4, Cd36, Ucp2, Pxmp4). Furthermore, several putative novel PPAR targets were identified that were commonly regulated in both species, including CREB3L3, KLF10, KLF11 and MAP3K8. Our results suggest that PPAR activation has a major impact on gene regulation in human hepatocytes. Importantly, the role of PPAR as master regulator of hepatic lipid metabolism is generally well-conserved between mouse and human. Overall, however, PPAR regulates a mostly divergent set of genes in mouse and human hepatocytes.
Publication Title
Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.
Sample Metadata Fields
Sex, Age, Specimen part, Subject, Time
View Samples- Mus musculus
- 32 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Elevated circulating triglycerides, which are considered a risk factor for cardiovascular disease, can be targeted by treatment with fenofibrate or fish oil. To gain insight into underlying mechanisms, we carried out a comparative transcriptomics and metabolomics analysis of the effect of 2 week treatment withfenofibrate and fish oil in mice. Plasma triglycerides were significantly decreased byfenofibrate (-49.1%) and fish oil (-21.8%), whereas plasma cholesterol was increased by fenofibrate (+29.9%) and decreased by fish oil (-32.8%). Levels of various phospholipid species were specifically decreased by fish oil, while levels of Krebs cycle intermediates were increased specifically by fenofibrate. Plasma levels of many amino acids were altered by fenofibrate and to a lesser extent by fish oil. Both fenofibrate and fish oil upregulated genes involved in fatty acid metabolism, and downregulated genes involved in blood coagulation and fibrinolysis. Significant overlap in gene regulation by fenofibrate and fish oil was observed, reflecting their property as high or low affinity agonist for PPAR, respectively. Fenofibrate specifically downregulated genes involved in complement cascade and inflammatory response. Fish oil specifically downregulated genes involved in cholesterol and fatty acid biosynthesis, and upregulated genes involved in amino acid and arachidonic acid metabolism. Taken together, the data indicate that despite being similarly potent towards modulating plasma free fatty acids, cholesterol and triglyceride levels, fish oil causes modest changes in gene expression likely via activation of multiple mechanistic pathways, whereas fenofibrate causes pronounced gene expression changes via a single pathway, reflecting the key difference between nutritional and pharmacological intervention.
Publication Title
Comparative transcriptomic and metabolomic analysis of fenofibrate and fish oil treatments in mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Homo sapiens
- 22 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Studies in mice have shown that PPAR is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPAR in human liver. Here we set out to compare the function of PPAR in mouse and human hepatocytes via analysis of target gene regulation. Primary hepatocytes from 6 human and 6 mouse donors were treated with PPAR agonist Wy14643 and gene expression profiling was performed using Affymetrix GeneChips followed by a systems biology analysis. Baseline PPAR expression was similar in human and mouse hepatocytes. Depending on species and time of exposure, Wy14643 significantly induced the expression of 362-672 genes. Surprisingly minor overlap was observed between the Wy14643-regulated genes from mouse and human, although more substantial overlap was observed at the pathway level. Xenobiotics metabolism and apolipoprotein synthesis were specifically regulated by PPAR in human hepatocytes, whereas glycolysis-gluconeogenesis was regulated specifically in mouse hepatocytes. Most of the genes commonly regulated in mouse and human were involved in lipid metabolism and many represented known PPAR targets, including CPT1A, HMGCS2, FABP, ACSL, and ADFP. Several genes were identified that were specifically induced by PPAR in human (MBL2, ALAS1, CYP1A1, TSKU) or mouse (Fbp2, lgals4, Cd36, Ucp2, Pxmp4). Furthermore, several putative novel PPAR targets were identified that were commonly regulated in both species, including CREB3L3, KLF10, KLF11 and MAP3K8. Our results suggest that PPAR activation has a major impact on gene regulation in human hepatocytes. Importantly, the role of PPAR as master regulator of hepatic lipid metabolism is generally well-conserved between mouse and human. Overall, however, PPAR regulates a mostly divergent set of genes in mouse and human hepatocytes.
Publication Title
Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.
Sample Metadata Fields
Sex, Age, Specimen part, Subject, Time
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Studies in mice have shown that PPAR is an important regulator of hepatic lipid metabolism and the acute phase response. However, little information is available on the role of PPAR in human liver. Here we set out to compare the function of PPAR in mouse and human hepatocytes via analysis of target gene regulation. Primary hepatocytes from 6 human and 6 mouse donors were treated with PPAR agonist Wy14643 and gene expression profiling was performed using Affymetrix GeneChips followed by a systems biology analysis. Baseline PPAR expression was similar in human and mouse hepatocytes. Depending on species and time of exposure, Wy14643 significantly induced the expression of 362-672 genes. Surprisingly minor overlap was observed between the Wy14643-regulated genes from mouse and human, although more substantial overlap was observed at the pathway level. Xenobiotics metabolism and apolipoprotein synthesis were specifically regulated by PPAR in human hepatocytes, whereas glycolysis-gluconeogenesis was regulated specifically in mouse hepatocytes. Most of the genes commonly regulated in mouse and human were involved in lipid metabolism and many represented known PPAR targets, including CPT1A, HMGCS2, FABP, ACSL, and ADFP. Several genes were identified that were specifically induced by PPAR in human (MBL2, ALAS1, CYP1A1, TSKU) or mouse (Fbp2, lgals4, Cd36, Ucp2, Pxmp4). Furthermore, several putative novel PPAR targets were identified that were commonly regulated in both species, including CREB3L3, KLF10, KLF11 and MAP3K8. Our results suggest that PPAR activation has a major impact on gene regulation in human hepatocytes. Importantly, the role of PPAR as master regulator of hepatic lipid metabolism is generally well-conserved between mouse and human. Overall, however, PPAR regulates a mostly divergent set of genes in mouse and human hepatocytes.
Publication Title
Comparative analysis of gene regulation by the transcription factor PPARalpha between mouse and human.
Sample Metadata Fields
Sex, Age, Specimen part, Time
View Samples- Homo sapiens
- 35 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
Background: Exercise has a positive effect on overall health. This study was performed to get an overview of the effects of mixed exercise training on skeletal muscl
Publication Title
Identification of human exercise-induced myokines using secretome analysis.
Sample Metadata Fields
Sex, Age, Race
View Samples