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GSE42902
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- Homo sapiens
- 37 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
We performed genome-wide methylation analysis of primary feto-placental arterial and venous endothelial cells from healthy (AEC and VEC) and GDM complicated pregnancies (dAEC and dVEC). Parallel transcriptome analysis identified variation in gene expression linked to GDM-associated DNA methylation, implying a direct functional link. Pathway analysis found that genes altered by exposure to GDM clustered to functions associated with Cell Morphology and Cellular Movement in both AEC and VEC. Further functional analysis demonstrated that GDM exposed cells have altered actin organization and barrier function.
Publication Title
Human fetoplacental arterial and venous endothelial cells are differentially programmed by gestational diabetes mellitus, resulting in cell-specific barrier function changes.
Sample Metadata Fields
Specimen part
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- Homo sapiens
- 10 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Spinal muscular atrophy (SMA) is one of the most common inherited forms of neurological disease leading to infant mortality. Patients exhibit selective loss of lower motor neurons resulting in muscle weakness, paralysis, and often death. Although patient fibroblasts have been used extensively to study SMA, motor neurons have a unique anatomy and physiology which may underlie their vulnerability to the disease process. Here we report the generation of induced pluripotent stem (iPS) cells from skin fibroblast samples taken from a child with SMA. These cells expanded robustly in culture, maintained the disease genotype, and generated motor neurons that showed selective deficits compared to those derived from the childs unaffected mother. This is the first study to show human iPS cells can be used to model the specific pathology seen in a genetically inherited disease. As such, it represents a promising resource to study disease mechanisms, screen novel drug compounds, and develop new therapies.
Publication Title
Induced pluripotent stem cells from a spinal muscular atrophy patient.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 15 Downloadable Samples
Illumina HiSeq 2500
Description
Intra-islet crosstalk between islet cells is critical in orchestrating the body’s response to changes in blood glucose levels, but is incompletely understood. In this study, we used transgenic mouse lines that allowed the purification and transcriptomic characterisation of alpha, beta, and delta cells, yielding an RNA-sequencing database that can be searched for regulatory proteins which are differentially expressed between cell types. As an illustrative example, we examined the expression of g-protein coupled receptors, and found that the ghrelin receptor, Ghsr, was highly expressed in delta cells compared to alpha and beta cells. GHSR excitation elicited increases in cytosolic calcium levels in primary delta cells. In the perfused pancreas, the application of ghrelin stimulated somatostatin secretion, correlating with a decrease in insulin and glucagon release, which was sensitive to somatostatin receptor antagonism. These results show that ghrelin acts specifically on delta cells within pancreatic islets to affect blood glucose regulation. Overall design: Examination of transcriptomic profiles obtained from pancreatic alpha, beta and delta cells
Publication Title
Transcriptomic profiling of pancreatic alpha, beta and delta cell populations identifies delta cells as a principal target for ghrelin in mouse islets.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Homo sapiens
- 151 Downloadable Samples
- Illumina HumanWG-6 v3.0 expression beadchip
Description
We compared the prognostic significance of ectodomain isoforms of the epidermal growth factor receptor (EGFR), which lack the tyrosine kinase (TK) domain, with that of the full length receptor and its autophosphorylation status in cervical cancers treated with conventional chemoradiotherapy.
Publication Title
Membranous expression of ectodomain isoforms of the epidermal growth factor receptor predicts outcome after chemoradiotherapy of lymph node-negative cervical cancer.
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
We compare transcriptomic profiles of human induced pluripotent stem cells (iPSCs), motor neurons (MNs) in vitro differentiated from iPSCs or human ESCs containing a HB9::GFP reporter for MNs, and human fetal spinal cords.
Publication Title
ALS disrupts spinal motor neuron maturation and aging pathways within gene co-expression networks.
Sample Metadata Fields
Sex
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- 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- Mus musculus
- 15 Downloadable Samples
- Illumina HiSeq 2000
Description
Nurr1 (Nr4a2, nuclear receptor subfamily 4 group A member 2) is needed for the development of ventral midbrain dopaminergic neurons, and has been associated with Parkinson''s disease. We used mice where the Nurr1 gene is ablated by tamoxifen treatment selectively in dopaminergic neurons. As a control, we used tamoxifen-treated mice where Nurr1 is not ablated. By laser microdissection of neurons selected by their TH1 (Th1l, TH1-like homolog) gene expression, we selected dopaminergic neurons for RNA extraction and high-throughput mRNA sequencing, in order to identify genes regulated by Nurr1. We found the main functional category of Nurr1-regulated genes are the nuclear-encoded mitochondrial genes. Overall design: Dopaminergic neurons with or without Nurr1 knocked out. TH-positive neurons were laser capture microdissected from cryostat coronal sections of the midbrain.
Publication Title
Transcription factor Nurr1 maintains fiber integrity and nuclear-encoded mitochondrial gene expression in dopamine neurons.
Sample Metadata Fields
Specimen part, Subject
View Samples