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SRP115904
Homo sapiens
36 Downloadable Samples
Illumina HiSeq 2500
Description
We discovered a rare missense mutation in NR1H4 (R436H), which encodes the farnesoid X receptor (FXR), associating with lower levels of total cholesterol in the Icelandic population. To explore the effects of R436H we used CRISPR-Cas9 to generate homozygous NR1H4 R436H and NR1H4 knockout human iPSC lines which we differentiated to hepatocytes. Hepatocytes were treated with an FXR agonist for 24 hours and transcript abundance measured by RNA-seq. The global response to FXR activation in NR1H4 R436H cells was very similar to that of wild-type cells showing that it is not a loss-of-function mutation. However, we did observe subtle gene expression differences compatible with an effect on lipids when we compared R436H agonist treated hepatocytes to wild-type agonist treated hepatocytes. Overall design: RNA-seq was performed on wild-type, NR1H4 knockout and NR1H4 R436H iPSC-derived hepatocytes treated with FXR agonist GW4064.
Publication Title
Predicted loss and gain of function mutations in ACO1 are associated with erythropoiesis.
Sample Metadata Fields
Specimen part, Treatment, Subject
View Samples- Homo sapiens
- 16 Downloadable Samples
Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
Glucocorticoid excess is linked to central obesity, adipose tissue insulin resistance and type 2 diabetes mellitus. The aim of our study was to investigate the effects of dexamethasone on gene expression in human subcutaneous and omental adipose tissue, in order to identify potential novel mechanisms and biomarkers for glucocorticoid-induced insulin resistance in adipose tissue. Dexamethasone changed the expression of 527 genes in both subcutaneous and omental adipose tissue. FKBP5 and CNR1 were the most responsive genes in both depots (~7-fold increase). Dexamethasone increased FKBP5 gene and protein expression in a dose-dependent manner in both depots, but FKBP5 protein levels were 10-fold higher in omental than subcutaneous adipose tissue. FKBP5 gene expression in subcutaneous adipose tissue was positively correlated with serum insulin, HOMA-IR and subcutaneous adipocyte diameter, while fold change in gene expression by dexamethasone was negatively correlated with clinical markers of insulin resistance, i.e. HbA1c, BMI, HOMA-IR and serum insulin. Only one gene, SERTM1, clearly differed in response to dexamethasone between the two depots. Dexamethasone at high concentrations, influences gene expression in both subcutaneous and omental adipose tissue in a similar pattern and promotes gene expression of FKBP5, a gene that may be implicated in glucocorticoid-induced insulin resistance.
Publication Title
FKBP5 expression in human adipose tissue increases following dexamethasone exposure and is associated with insulin resistance.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Mus musculus
- 24 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
BACKGROUND: The transcript levels of many genes exhibit significant variation in tissue samples from inbred laboratory mice. A microarray experiment was designed to separate transcript abundance variation across samples from adipose, heart, kidney, and liver tissues of C57BL/6J mice into within-mouse and between-mouse components. Within-mouse variance captures variation due to heterogeneity of gene expression within tissues, RNA-extraction, and array processing. Between-mouse variance reflects differences in transcript levels between these genetically identical mice. Many biological sources can contribute to heterogeneous transcript levels within a tissue sample including inherent stochasticity of biochemical processes such as intrinsic and extrinsic noise within cells and differences in cell-type composition which can result from heterogeneity of stem and progenitor cell populations. Differences in global signaling patterns between individuals and micro-environmental influences such as interactions with pathogens and cage mates can also contribute to variation, but are likely to contribute more to the between-mouse variance component.
Publication Title
Stochastic variation of transcript abundance in C57BL/6J mice.
Sample Metadata Fields
Sex, Age, Specimen part
View Samples- Saccharomyces cerevisiae
- 6 Downloadable Samples
- Illumina Genome Analyzer IIx
Description
Anti-sense non-coding transcripts, genes-within-genes, and convergent gene pairs are prevalent among eukaryotes. The existence of such transcription units raises the question of what happens when RNA polymerase II (RNAPII) molecules collide head-to-head. Here we use a combination of biochemical and genetic approaches in yeast to show that polymerases transcribing opposite DNA strands cannot bypass each other. RNAPII stops, but does not dissociate upon head-to-head collision in vitro, suggesting that opposing polymerases represent insurmountable obstacles for each other. Head-to-head collision in vivo results in RNAPII stopping as well, and removal of collided RNAPII from the DNA template can be achieved via ubiquitylation-directed proteolysis. Indeed, in cells lacking efficient RNAPII poly-ubiquitylation, the half-life of collided polymerases increases, so that these can be detected between convergent genes by ChIP-Seq. These results provide new insight into fundamental mechanisms of gene traffic control, and point to an unexplored effect of anti-sense transcription on gene regulation via polymerase collision. Overall design: Total RNA was extracted from WT or Elongin C deletion mutant (elc1?) cells and strand-specific RNA-Seq was performed. Three biological replicates were performed for WT and elc1?.
Publication Title
RNA polymerase II collision interrupts convergent transcription.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 4 Downloadable Samples
Affymetrix Human Genome U133A Array (hgu133a)
Description
Neural progenitor cells (hNPC) derived from the developing human brain can be expanded in culture and subsequently differentiated into neurons and glia. They provide an interesting source of tissue for both modeling brain development and future cellular replacement therapies. It is becoming clear that hNPC are regionally and temporally specified depending on which brain region they were isolated from and its developmental stage. We show here that hNPC derived from the developing cortex (hNPCCTX) and ventral midbrain (hNPCVM) have similar morphological characteristics and express the progenitor cell marker nestin. However, hNPCCTX cultures were highly proliferative and produced large numbers of neurons, while hNPCVM divided slowly and produced less neurons but more astrocytes. Microarray analysis revealed a similar expression pattern for some stemness markers between the two growing cultures, overlaid with a regionally specific profile that identified some important differentially expressed neurogenic transcription factors. By over expressing one of these, the transcription factor ASCL1, we were able to regain neurogenesis from hNPCVM cultures which produced larger neurons with more neurites than hNPCCTX, but no fully mature dopamine neurons. Thus hNPC are regionally specified and can be induced to undergo neurogenesis following genetic manipulation. While this restores neuronal production with a region specific phenotype, it does not restore full neurochemical maturation which may require additional factors.
Publication Title
Regionally specified human neural progenitor cells derived from the mesencephalon and forebrain undergo increased neurogenesis following overexpression of ASCL1.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Expression 430B Array (moe430b), Affymetrix Mouse Expression 430A Array (moe430a)
Description
Treatment of gonadectomized mice with estradiol, dihydrotestosterone or vehicle to compare gene expression in gastrocnemius.
Publication Title
Stimulation of both estrogen and androgen receptors maintains skeletal muscle mass in gonadectomized male mice but mainly via different pathways.
Sample Metadata Fields
Sex, Specimen part, Disease, Compound
View Samples- Homo sapiens
- 19 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
These samples have been analyzed for global alternative splicing variation on exon-level expression data using the FIRMA algorithm. We have identified and described transcriptome instability as a genome-wide, pre-mRNA splicing related characteristic of solid cancers.
Publication Title
Transcriptome instability as a molecular pan-cancer characteristic of carcinomas.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 9 Downloadable Samples
- Illumina HiSeq 2000
Description
Staphylococcus aureus enterotoxins cause debilitating systemic inflammatory responses, but how they spread systemically and trigger cascading inflammation is unclear. Here, we showed in mice that after inhalation, Staphylococcus aureus enterotoxin A rapidly entered the bloodstream and induced T cells to orchestrate systemic recruitment of inflammatory monocytes and neutrophils. To study the mechanism used by specific T cells that mediate this process, a systems approach revealed inducible and non-inducible pathways as potential targets. It was found that TNF induced neutrophil entry into the peripheral blood, while CD28 signaling, but not TNF, was needed for chemotaxis of inflammatory monocytes into blood and lymphoid tissue. However, both pathways triggered local recruitment of neutrophils into lymph nodes. Thus, our findings revealed a dual mechanism of monocyte and neutrophil recruitment by T cells relying on overlapping and non-overlapping roles for the non-inducible costimulatory receptor CD28 and the inflammatory cytokine TNF. During sepsis, there might be clinical value in inhibiting CD28 signaling to decrease T cell-mediated inflammation and recruitment of innate cells while retaining bioactive TNF to foster neutrophil circulation. Overall design: The purpose of this analysis was to determine changes in gene expression in SEA-specific Vß3+ T cells and bystander T Vß14+ cells 40 min after SEA or vehicle inhalation.The samples were collected from three independent experiments with total n=3 per group. Three groups of samples were prepared: vehicle Vß3+ T cells, SEA Vß3+ T cells, and SEA Vß14+ T cells.
Publication Title
TNF and CD28 Signaling Play Unique but Complementary Roles in the Systemic Recruitment of Innate Immune Cells after Staphylococcus aureus Enterotoxin A Inhalation.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 348 Downloadable Samples
- Illumina HiSeq 2000
Description
Genetic variation governs protein expression through both transcriptional and post-transcriptional processes. To investigate this relationship, we combined a multiplexed, mass spectrometry-based method for protein quantification with an emerging mouse model harboring extensive genetic variation from 8 founder strains. We collected genome-wide mRNA and protein profiling measurements to link genetic variation to protein expression differences in livers from 192 Diversity Outcross mice. Overall design: Illumina 100bp single-end liver RNA-seq from 192 male and female Diversity Outbred 26-week old mice raised on standard chow or high fat diet. Each sample was sequenced in 2x technical replicates across multiple flowcells. Samples were randomly assigned lanes and multiplexed at 12-24x.
Publication Title
Epistatic Networks Jointly Influence Phenotypes Related to Metabolic Disease and Gene Expression in Diversity Outbred Mice.
Sample Metadata Fields
Sex, Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 331 Downloadable Samples
- Affymetrix Human Exon 1.0 ST Array [transcript (gene) version (huex10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptome instability in colorectal cancer identified by exon microarray analyses: Associations with splicing factor expression levels and patient survival.
Sample Metadata Fields
Specimen part
View Samples