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GSE19877
Rattus norvegicus
11 Downloadable Samples
Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
The global prevalence of obesity is increasing across age and gender. The rising burden of obesity in young people contributes to the early emergence of type 2 diabetes. Having one parent obese is an independent risk factor for childhood obesity. While the detrimental impact of diet-induced maternal obesity on offspring is well established, the extent of the contribution of obese fathers is unclear, as is the role of non-genetic factors in the casual pathway. Here we show that paternal high fat diet exposure programmed -cell dysfunction in their F1 female offspring. Chronic high fat diet consumption in Sprague Dawley fathers led to increased body weight, adiposity, impaired glucose tolerance and insulin sensitivity. Relative to controls, their female offspring had lower body weight at day-1, increased pubertal growth rate, impaired insulin secretion and glucose tolerance, in the absence of obesity or increased adiposity. Paternal high fat diet was observed to alter gene expression of pancreatic islet genes in adult female offspring (P < 0.001); affected functional clusters includes calcium ion binding, insulin, apoptosis, Wnt and cell cycle organ/system development. This is the first reported study in mammals describing non-genetic, intergenerational transmission of metabolic sequelae of high fat diet from father to offspring. These findings support a role of fathers in metabolic programming of offspring and form a framework for further studies.
Publication Title
Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring.
Sample Metadata Fields
Sex
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
NPY signalling via osteoblastic Y1 receptors has been shown to control bone mass but also contributes significantly to the control of whole-body insulin secretion and glucose homeostasis in mice through the release of novel factor(s) which are different from the previously implicated osteocalcin.
Publication Title
Osteoglycin, a novel coordinator of bone and glucose homeostasis.
Sample Metadata Fields
Sex, Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
We found that in rodents, b-cell mass expansion during pregnancy and obesity is associated with changes in the expression of a group of islet microRNAs. We were able to reproduce in isolated pancreatic islets the decrease of miR-338-3p level observed in gestation and obesity by activating the G-protein coupled estrogen receptor GPR30 and the GLP1 receptor. Blockade of miR-338-3p in b-cells using specific anti-miR molecules mimicked gene expression changes occurring during b-cell mass expansion and resulted in increased proliferation and improved survival both in vitro and in vivo. These findings point to a major role for miR-338-3p in compensatory b-cell mass expansion occurring under different insulin resistance states.
Publication Title
MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Homo sapiens
- 10 Downloadable Samples
IlluminaHiSeq2500
Description
LMO2 is a component of multisubunit DNA-binding transcription factor complexes that regulate gene expression in hematopoietic stem and progenitor cell development. Enforced expression of LMO2 causes leukemia by inducing hematopoietic stem cell-like features in T-cell progenitor cells, but the biochemical mechanisms of LMO2 function have not been fully elucidated. In this study we systematically dissected the LMO2/LDB1 binding interface to investigate the role of this interaction in T-cell leukemia. Alanine scanning mutagenesis of the LIM interaction domain of LDB1 revealed a discrete motif R320LITR required for LMO2 binding. Most strikingly, co-expression of full length, wild type LDB1 increased LMO2 steady state abundance, whereas co-expression of mutant proteins deficient in LMO2 binding compromised LMO2 stability. These mutant LDB1 proteins also exerted dominant negative effects on growth and transcription in diverse leukemic cell lines. Raw gene expression data on HSB-2 cells is presented here. Overall design: RNAseq were performed on HSB cell lines to examine their expression patterns
Publication Title
LMO2 Oncoprotein Stability in T-Cell Leukemia Requires Direct LDB1 Binding.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 87 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Stability of gene expression in human T cells in different gravity environments is clustered in chromosomal region 11p15.4.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 63 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Dynamic gene expression response to altered gravity in human T cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 39 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
We investigated differentially regulated genes in human Jurkat T lymphocytic cells in 20s and 5min microgravity and in hypergravity and compared expression profiles to identify potential gravity-regulated genes and adaptation processes.
Publication Title
Dynamic gene expression response to altered gravity in human T cells.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
We investigated differentially regulated and stably expressed genes in human Jurkat T lymphocytic cells in 5min simulated microgravity and hypergravity and compared expression profiles to identify gravity-regulated and unaffected genes as well as adaptation processes.
Publication Title
Stability of gene expression in human T cells in different gravity environments is clustered in chromosomal region 11p15.4.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Transcriptome Array 2.0 (hta20)
Description
We investigated differentially regulated genes in human Jurkat T lymphocytic cells in 20s and 5min microgravity and in hypergravity and compared expression profiles to identify potential gravity-regulated genes and adaptation processes.
Publication Title
Dynamic gene expression response to altered gravity in human T cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
The short chain fatty acid (SCFA) receptor (free fatty acid receptor-3; FFAR3) is expressed in pancreatic beta cells; however, its role in insulin secretion is not clearly defined. Here, we examined the role of FFAR3 in insulin secretion. Using islets from global knockout FFAR3 (Ffar3-/-) mice, we explored the role of FFAR3 and ligand-induced FFAR3 signaling on glucose stimulated insulin secretion. RNA sequencing was also performed to gain greater insight into the impact of FFAR3 deletion on the islet transcriptome. First exploring insulin secretion, it was determined that Ffar3-/- islets secrete more insulin in a glucose-dependent manner as compared to wildtype (WT) islets. Next, exploring its primary endogenous ligand, propionate, and a specific agonist for FFAR3, signaling by FFAR3 inhibited glucose-dependent insulin secretion, which occurred through a Gai/o pathway. To help understand these results, transcriptome analyses by RNA-sequencing of Ffar3-/- and WT islets observed multiple genes with well known roles in islet biology to be altered by genetic knockout of FFAR3. Our data shows that FFAR3 signaling mediates glucose stimulated insulin secretion through Gai/o sensitive pathway. Future studies are needed to more rigorously define the role of FFAR3 by in vivo approaches. Overall design: Analysis of total RNA from 3 biological replicates of pancreatic islets isolated from free fatty acid receptor 3 knockout (Ffar3 KO) and wildtype (Ffar3 WT) male mice
Publication Title
FFAR3 modulates insulin secretion and global gene expression in mouse islets.
Sample Metadata Fields
No sample metadata fields
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