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.
Transcription factor Nurr1 maintains fiber integrity and nuclear-encoded mitochondrial gene expression in dopamine neurons.
Specimen part, Subject
View SamplesGlucocorticoid 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.
FKBP5 expression in human adipose tissue increases following dexamethasone exposure and is associated with insulin resistance.
Sex, Age, Specimen part
View SamplesBACKGROUND: 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.
Stochastic variation of transcript abundance in C57BL/6J mice.
Sex, Age, Specimen part
View SamplesTreatment of gonadectomized mice with estradiol, dihydrotestosterone or vehicle to compare gene expression in gastrocnemius.
Stimulation of both estrogen and androgen receptors maintains skeletal muscle mass in gonadectomized male mice but mainly via different pathways.
Sex, Specimen part, Disease, Compound
View SamplesGenetic 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.
Epistatic Networks Jointly Influence Phenotypes Related to Metabolic Disease and Gene Expression in Diversity Outbred Mice.
Sex, Specimen part, Cell line, Subject
View SamplesAnalysis of tissues of DBA/2 mice fed a standard breeding diet (SBD) and high fat diet (HFD) revealed tissue specific roles in inflammation and disease, and altered communication between tissues. The tissues surveyed incuded adipose tissues (brown, inguinal, mesenteric, retro-peritoneal, subcutaneious and gonadal), muscle and liver.
High-fat diet leads to tissue-specific changes reflecting risk factors for diseases in DBA/2J mice.
Specimen part, Treatment
View SamplesNeural progenitor cells (NPCs) have regenerative capabilities that are activated during inflammation. By measuring the global transcriptome and performing functional studies, we aimed at elucidating if and how NPCs from the non-germinal niche of the spinal cord differ from germinal niche NPCs, here represented by the subventricular zone (SVZ) NPCs. Moreover, we investigated how these cells are affected by chronic inflammation modeled by Experimental Autoimmune Encephalomyelitis (EAE). NPCs were isolated and propagated from the SVZ and cervical, thoracic and caudal regions of the spinal cord from healthy rats and rats subjected to EAE. Using Affymetrix microarray analyses, the global transcriptome was measured in the different NPC populations both in undifferentiated and differentiated cultures. These analyses were paralleled by differentiation studies and quantitative RT-PCR of differentiation-specific genes.
Change of fate commitment in adult neural progenitor cells subjected to chronic inflammation.
Specimen part, Disease, Disease stage
View SamplesMesenchymal stem cells (MSCs) and their cellular response to various stimuli have been characterized in great detail in culture conditions. In contrast, the cellular response of MSCs in an in vivo setting is still uncharted territory. In this study, we investigated the cellular response of MSCs following transplantation into spinal cord injury (SCI).Mouse bone marrow-derived MSCs were transplanted 24h following severe contusion SCI in mice. As controls, MSCs transplanted to uninjured spinal cord and non-transplanted MSCs were used. At seven days post transplantation, the MSCs were isolated from the SCI, and their global transcriptional changes investigated using RNA-sequencing. We found that MSCs transplanted into SCI down-regulate their response to cytokines, tendency to adhere and to undergo phagocytosis but up-regulate their ability to repair DNA and proliferate. Overall design: Evaluation of transcriptional changes in transplanted mesenchymal stem cells.
Mesenchymal stem cells transplanted into spinal cord injury adopt immune cell-like characteristics.
Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Array profiling reveals contribution of Cthrc1 to growth of the denervated rat urinary bladder.
Sex, Specimen part
View SamplesDifferent human adipose tissue depots may have functional differences. Subcutaneous human adipose tissue has been extensively studied, but less is known about other depots. Perithyroid (PT) adipose tissue contains not only white adipocytes but also brown adipocytes. The aim of this study was to compare the expression of brown adipocyte containing perithyroid adipose tissue with s.c. adipose tissue.role in the development of obesity. Expression profiling of adipose tissue may give insights into mechanisms contributing to obesity and obesity-related disorders.
Gene expression in human brown adipose tissue.
Sex, Specimen part
View Samples