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GSE61381
Macaca fascicularis
6 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
The LXR-regulated E3 ubiquitin ligase IDOL controls LDLR receptor stability independent of SREBP and PCSK9, but its relevance to plasma lipid levels is unknown. Here we demonstrate that the effects of the LXRIDOL axis are both tissue- and species-specific. In mice, LXR agonist induces Idol expression in peripheral tissues but not in liver, and does not change plasma LDL levels. Accordingly, Idol-deficient mice exhibit elevated LDLR protein levels in peripheral tissues but not in the liver and have minimal change in plasma LDL levels. By contrast, LXR activation in cynomolgus monkeys induces hepatic IDOL expression, reduces LDLR protein, and raises plasma LDL levels. Knockdown of IDOL in monkeys with an antisense oligonucleotide blunts the effect of LXR agonist on LDL levels. These results implicate IDOL as a modulator of plasma lipid levels in primates and support further investigation into IDOL inhibition as a strategy for LDL lowering in humans.
Publication Title
The LXR-Idol axis differentially regulates plasma LDL levels in primates and mice.
Sample Metadata Fields
Specimen part, Treatment
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
View Samples- Mus musculus
- 12 Downloadable Samples
- Illumina HiSeq 2000
Description
We report downstream gene expression changes in stem cells of the adult mouse hair follicle upon conditional ablating of the transcription factor Forkhead Box C1 transcription factor (FOXC1). Hair follicles undergo cycles of rest (telogen; Tel) and regeneration (anagen; Ana). As such, we performed our analysis on these two different stages of hair follicles. Overall design: mRNA-sequencing of WT vs. Foxc1-conditional or inducible KO (Foxc1-cKO or iKO) hair follicle stem cells (HFSCs) purified from mouse dorsal back skin by flow-activated cell sorting (FACS).
Publication Title
FOXC1 maintains the hair follicle stem cell niche and governs stem cell quiescence to preserve long-term tissue-regenerating potential.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Background & Aims: MiRNAs are small (~22 nucleotide), non-coding RNA molecules that regulate gene expression through imperfect complementarity with target messenger RNAs. The function of miRNA in mammalian organogenesis is largely unknown. Conditional loss-of-function of Dicer, the enzyme that processes precursor miRNA transcripts into their mature, active form, has been shown to cause severe defects in a number of organ systems. Here we address the role of Dicer in liver development and function. Methods: Mice lacking Dicer function in hepatocytes were generated using an Afp-Cre strain to drive deletion of a floxed Dicer allele. Deletion of the flox-dicer allele was confirmed by quantitative PCR. Decreased miRNA levels detected by quantitative RT-PCR and in situ hybridization confirmed loss of Dicer function. Gene expression microarray analysis was performed on liver RNA from P28 mutant and control mice. Liver sections from mutant and control mice ranging from embryonic stages through 3-4 months of age were examined and liver function tests were performed on adult mice. Results: Mice lacking hepatocyte Dicer function were born alive at the expected frequency, and had grossly normal appearance and behavior. Despite the loss of mature miRNA, hepatic function was normal, as reflected by normal blood gludose, albumin, cholesterol, and bilirubin. However, mutant mice between 2-4 months of age exhibit progressive hepatocyte damage, elevated ALT/AST, with evidence of balanced proliferation and apoptosis in the lobule. Microarray analysis indicates large-scale changes in gene expression, with increased expression of many miRNA targets, as well as imprinted genes. Conclusions: Loss of miRNA processing in the liver at late gestation has a remarkably mild phenotype, suggesting that miRNAs do not play an essential role in hepatic physiology. However, miRNA deficiency results in hepatocyte apoptosis and balanced hepatocyte regeneration. Finally, microarray analysis of gene expression in mutant liver suggests a previously unrecognized role for Dicer in the repression of imprinted genes.
Publication Title
Hepatic function is preserved in the absence of mature microRNAs.
Sample Metadata Fields
Age, Specimen part
View Samples