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GSE17269
Homo sapiens
5 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The homeostasis of circulating B cell subsets in the peripheral blood of healthy adults is well regulated, but in disease it can be severely disturbed. Thus, a subgroup of patients with common variable immunodeficiency (CVID) presents with an extraordinary expansion of an unusual B cell population characterized by the low expression of CD21. Since these circulating atypical B cells in the blood of CVID patients could not be assigned to any certain B cell differentiation stage in the periphery, they were designated as CD21low B cells. Although, CD21low B cells are polyclonal and unmutated IgM+IgD+ B cells like naive B cells in the peripheral blood, they reveal several distinct phenotypic and functional features.
Publication Title
Circulating CD21low B cells in common variable immunodeficiency resemble tissue homing, innate-like B cells.
Sample Metadata Fields
Specimen part, Disease
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- 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- Danio rerio
- 12 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A zebrafish transgenic model of Ewing's sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 6 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
The fusion oncoprotein EWS-FLI1 arises from a t(11;22)(q24;q12) chromosomal translocation and causes Ewing's Sarcoma, a malignant bone tumor. The mechanism whereby EWS-FLI1 transforms cells is unknown. Somatic, mosaic expression of human EWS-FLI1 in zebrafish from the heat shock promoter [Tg(HSP:EWS-FLI1)] caused small round blue cell tumors (SRBCTs) similar to human Ewing's sarcoma.
Publication Title
A zebrafish transgenic model of Ewing's sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis.
Sample Metadata Fields
Specimen part
View Samples- Danio rerio
- 6 Downloadable Samples
- Affymetrix Zebrafish Genome Array (zebrafish)
Description
The fusion oncoprotein EWS-FLI1 arises from a t(11;22)(q24;q12) chromosomal translocation and causes Ewing's Sarcoma, a malignant bone tumor. The mechanism whereby EWS-FLI1 transforms cells is unknown. We made germline transgenic zebrafish expressing human EWS-FLI1 under the control of the heat shock promoter. Induction of EWS-FLI1 expression causes multiple defects in embryonic development.
Publication Title
A zebrafish transgenic model of Ewing's sarcoma reveals conserved mediators of EWS-FLI1 tumorigenesis.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus, Homo sapiens, Rattus norvegicus
- 46 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Expression 430A Array (moe430a)
Description
PPARalpha is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPARalpha in hepatic lipid metabolism, many PPARalpha-dependent pathways and genes have yet to be discovered. In order to obtain an overview of PPARalpha-regulated genes relevant to lipid metabolism, and to probe for novel candidate PPARalpha target genes, livers from several animal studies in which PPARalpha was activated and/or disabled were analyzed by Affymetrix GeneChips. Numerous novel PPARalpha-regulated genes relevant to lipid metabolism were identified. Out of this set of genes, eight genes were singled out for study of PPARalpha-dependent regulation in mouse liver and in mouse, rat, and human primary hepatocytes, including thioredoxin interacting protein (Txnip), electron-transferring-flavoprotein beta polypeptide (Etfb), electron-transferring-flavoprotein dehydrogenase (Etfdh), phosphatidylcholine transfer protein (Pctp), endothelial lipase (EL, Lipg), adipose triglyceride lipase (Pnpla2), hormone-sensitive lipase (HSL, Lipe), and monoglyceride lipase (Mgll). Using an in silico screening approach, one or more PPAR response elements (PPREs) were identified in each of these genes. Regulation of Pnpla2, Lipe, and Mgll, which are involved in triglyceride hydrolysis, was studied under conditions of elevated hepatic lipids. In wild-type mice fed a high fat diet, the decrease in hepatic lipids following treatment with the PPARalpha agonist Wy14643 was paralleled by significant up-regulation of Pnpla2, Lipe, and Mgll, suggesting that induction of triglyceride hydrolysis may contribute to the anti-steatotic role of PPARalpha. Our study illustrates the power of transcriptional profiling to uncover novel PPARalpha-regulated genes and pathways in liver.
Publication Title
Comprehensive analysis of PPARalpha-dependent regulation of hepatic lipid metabolism by expression profiling.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302), Affymetrix Mouse Expression 430A Array (moe430a)
Description
PPAR is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPAR in hepatic lipid metabolism, many PPAR-dependent pathways and genes have yet to be discovered. In order to obtain an overview of PPAR-regulated genes relevant to lipid metabolism, and to probe for novel candidate PPAR target genes, livers from several animal studies in which PPAR was activated and/or disabled were analyzed by Affymetrix GeneChips. Numerous novel PPAR-regulated genes relevant to lipid metabolism were identified. Out of this set of genes, eight genes were singled out for study of PPAR-dependent regulation in mouse liver and in mouse, rat, and human primary hepatocytes, including thioredoxin interacting protein (Txnip), electron-transferring-flavoprotein polypeptide (Etfb), electron-transferring-flavoprotein dehydrogenase (Etfdh), phosphatidylcholine transfer protein (Pctp), endothelial lipase (EL, Lipg), adipose triglyceride lipase (Pnpla2), hormone-sensitive lipase (Lipe), and monoglyceride lipase (Mgll). Using an in silico screening approach, one or more PPAR response elements (PPREs) were identified in each of these genes. Since Pnpla2, Lipe, and Mgll contribute to hepatic triglyceride hydrolysis, gene regulation was studied under conditions of elevated hepatic lipids. In wild-type mice fed a high fat diet, the decrease in hepatic lipids following treatment with the PPAR agonist Wy14643 was paralleled by significant up-regulation of Pnpla2, Lipe, and Mgll, suggesting that induction of triglyceride hydrolysis may contribute to the anti-steatotic role of PPAR. Our study illustrates the power of transcriptional profiling to uncover novel PPAR-regulated genes and pathways in liver.
Publication Title
Comprehensive analysis of PPARalpha-dependent regulation of hepatic lipid metabolism by expression profiling.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Affymetrix Mouse Expression 430A Array (moe430a)
Description
PPAR is a ligand-activated transcription factor involved in the regulation of nutrient metabolism and inflammation. Although much is already known about the function of PPAR in hepatic lipid metabolism, many PPAR-dependent pathways and genes have yet to be discovered. In order to obtain an overview of PPAR-regulated genes relevant to lipid metabolism, and to probe for novel candidate PPAR target genes, livers from several animal studies in which PPAR was activated and/or disabled were analyzed by Affymetrix GeneChips. Numerous novel PPAR-regulated genes relevant to lipid metabolism were identified. Out of this set of genes, eight genes were singled out for study of PPAR-dependent regulation in mouse liver and in mouse, rat, and human primary hepatocytes, including thioredoxin interacting protein (Txnip), electron-transferring-flavoprotein polypeptide (Etfb), electron-transferring-flavoprotein dehydrogenase (Etfdh), phosphatidylcholine transfer protein (Pctp), endothelial lipase (EL, Lipg), adipose triglyceride lipase (Pnpla2), hormone-sensitive lipase (Lipe), and monoglyceride lipase (Mgll). Using an in silico screening approach, one or more PPAR response elements (PPREs) were identified in each of these genes. Since Pnpla2, Lipe, and Mgll contribute to hepatic triglyceride hydrolysis, gene regulation was studied under conditions of elevated hepatic lipids. In wild-type mice fed a high fat diet, the decrease in hepatic lipids following treatment with the PPAR agonist Wy14643 was paralleled by significant up-regulation of Pnpla2, Lipe, and Mgll, suggesting that induction of triglyceride hydrolysis may contribute to the anti-steatotic role of PPAR. Our study illustrates the power of transcriptional profiling to uncover novel PPAR-regulated genes and pathways in liver.
Publication Title
Comprehensive analysis of PPARalpha-dependent regulation of hepatic lipid metabolism by expression profiling.
Sample Metadata Fields
Sex, Specimen part
View Samples