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SRP117574
Mus musculus
4 Downloadable Samples
Illumina Genome Analyzer II
Description
Peroxisome proliferator-activated receptor ? (PPAR?) is the master regulator of adipocyte differentiation and is closely linked to the development of obesity. Despite a large progress on the transcriptional network of PPAR?, the epigenetic regulation associated with histone modification remains elusive. Here, we found that CDK2-associated cullin 1 (CACUL1), identified as a novel SIRT1 interacting protein, directly binds to PPAR? through the CoRNRbox 2 and represses the transcription activity and adipogenic potential of PPAR?. Upon CACUL1 depletion, less SIRT1 and more LSD1 was recruited to the PPAR?-responsive gene promoter, leading to the increased histone H3K9 acetylation and decreased H3K9 methylation for PPAR? activation during adipogenesis of 3T3-L1 cells. These findings were reversed upon fasting or resveratrol treatment. Further, gene expression profiling using RNA-seq supported the repressive role of CACUL1 in PPAR? activation and fat accumulation. Finally, we confirmed the CACUL1 function in human adipose-derived stem cells. Overall, our data suggest thatCACUL1 tightly regulates PPAR? signaling through the mutual opposition between SIRT1 and LSD1, providing additional insight into its use for anti-obesity treatment.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Cell line, Treatment
View Samples- Danio rerio
- 17 Downloadable Samples
Affymetrix Zebrafish Genome Array (zebrafish)
Description
microRNAs play crucial roles in the early development of an organism. However the regulation of transcription through the action of microRNAs during the initial embyonic development has not been studied.
Publication Title
miR-34 is maternally inherited in Drosophila melanogaster and Danio rerio.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 16 Downloadable Samples
- Illumina HiSeq 2500
Description
Overconsumption of high-fat diet (HFD) and sugar-sweetened beverages are risk factors for development of obesity, insulin resistance and fatty liver disease. To dissect mechanisms underlying this association, mice were fed chow or HFD with or without addition of fructose- or glucose-supplemented water. There were no physiological differences in mice supplemented with fructose or glucose on chow diet. Despite similar caloric intake, mice on HFD supplemented with fructose developed more pronounced obesity, glucose intolerance and hepatomegaly than glucose-supplemented mice. While both sugars increased Chrebp-?, fructose supplementation uniquely increased Srebp1c and downstream fatty acid synthesis genes resulting in reduced liver insulin signaling, whereas glucose enhanced total Chrebp expression and triglyceride synthesis but was associated with improved hepatic insulin signaling. Metabolomic and RNA sequence analysis confirmed dichotomous effects of fructose and glucose supplementation on liver metabolism in spite of inducing similar amount of hepatic lipid accumulation. Ketohexokinase, the first enzyme of fructose metabolism, was increased in fructose-fed mice and in obese adolescents with steatohepatitis. Knockdown of ketohexokinase-C in liver improved hepatic steatosis and glucose tolerance in fructose-supplemented mice. Thus, fructose is a component of dietary sugar that is uniquely associated with poor metabolic outcomes, while increased glucose intake may be protective.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part, Cell line
View Samples- Homo sapiens
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The proinflammatory cytokine, TNFalpha is critical in maintaining liver homeostasis since it is a major determiner of hepatocyte life and death. Considering this, gene transcription profiling was examined in control and TNFalpha treated HepG2 cells. Results indicated that TNFalpha could significantly alter the expression of a significant number of genes; most of them were functionally distributed among molecular functions like catalytic activity, binding, molecular transducer activity, transporter activity, translation and transcription regulator activities or enzyme regulator activity. Also, within genes up-regulated by TNFalpha, several GO terms related to lipid and fat metabolism were significantly overrepresented indicating global dysregulation of fat metabolism within the hepatocyte and those within the down-regulated dataset included genes involved in immunoglobulin receptor activity and IgE binding thereby indicating a compromise in immune defense mechanism(s) apart from those involved the DNA binding and protein binding categories. The interacting network of lipid metabolism, small molecule biochemistry was derived to be significantly affected that correlated well with the top canonical pathway of biosynthesis of steroids and molecular and cellular function of lipid metabolism. All these indicate TNFalpha to be significantly altering the transcriptome profiling within HepG2 cells with genes involved in lipid and steroid metabolism being the most favoured. This study suitably addresses the genes that determine TNFalpha mediated alterations within the hepatocyte mainly the phenotypes of hepatic steatosis and fatty liver that are associated with several hepatic pathological states.
Publication Title
Gene expression profiling and network analysis reveals lipid and steroid metabolism to be the most favored by TNFalpha in HepG2 cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Bos indicus
- 4 Downloadable Samples
- Affymetrix Bovine Genome Array (bovine)
Description
Hypobaric Hypoxia Induced Transcriptional profiling of Bovine (Bos indicus)
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Disease stage, Subject
View Samples- Danio rerio
- 14 Downloadable Samples
- IlluminaHiSeq1000
Description
RNA-seq data from control and MCT8 morphant zebrafish embryos at 25hpf
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Hsp27 can regulate multiply signaling pathway and protect HCC cells apoptosis by mediating interaction with its cochaperones
Publication Title
No associated publication
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 1 Downloadable Sample
Description
Investigate epigenetic mechanisms contributing to stemness/pluripotency in lung cancers and potentially identify novel therapeutic targets in these malignancies.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 12 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
TBR-760 (formerly BIM-23A760) is a chimeric dopamine (DA)-somatostatin (SST) compound with potent agonist activity at both DA type 2 (D2R) and SST type 2 (SSTR2) receptors. Non-functioning pituitary adenomas (NFPAs) express both D2R and SSTR2 and, consequently, may respond to TBR-760. We utilized a mouse model with the pro-opiomelanocortin (POMC) gene knocked-out that spontaneously develops aggressive NFPAs. Both genomic microarray and DA and SST receptor mRNA expression analysis indicate that POMC KO mouse tumors and human NFPAs have similar expression profiles, establishing POMC KO mice as a valid model for study of NFPAs. Treatment with TBR-760 for 8 weeks resulted in nearly complete inhibition of established tumor growth, whereas tumors from vehicle-treated mice increased in size by 890 ± 0.7%. These results support the development of TBR-760 as a therapy for patients with NFPA.
Publication Title
TBR-760, a Dopamine-Somatostatin Compound, Arrests Growth of Aggressive Nonfunctioning Pituitary Adenomas in Mice.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 62 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Evaluation of pretreatment gene expression profiling features in elderly CLL patients; correlation with clinical outcome
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part
View Samples