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GSE84500
Homo sapiens
48 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Gene Expression analysis of a differentiation timeseries of human Mesenchymal Stem Cells (hMSCs) in the presence of adipogenic/osteogenic factors. hMSCs differentiate into fat cells when treated with dexamethasone (10^-6 M), insulin (10 ug/ml), rosiglitazone (10^-7 M) and IBMX (250 uM). TGFbeta (5 ng/ml) inhibits this process and redirects these cells to differentiate into bone cells.
Publication Title
TGFβ-induced switch from adipogenic to osteogenic differentiation of human mesenchymal stem cells: identification of drug targets for prevention of fat cell differentiation.
Sample Metadata Fields
Specimen part, Treatment, Time
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Mesenchymal progenitor cells can be differentiated in vitro into myotubes that exhibit many characteristic features of primary mammalian skeletal muscle fibers. However, in general, they do not show the functional excitation-contraction coupling or the striated sarcomere arrangement typical of mature myofibers. Epigenetic modifications have been shown to play a key role in regulating the progressional changes in transcription necessary for muscle differentiation. In this study, we demonstrate that treatment of murine C2C12 mesenchymal progenitor cells with 10 M of the DNA methylation inhibitor 5-azacytidine (5AC) promotes myogenesis, resulting in myotubes with enhanced maturity as compared to untreated myotubes. Specifically, 5AC treatment resulted in the upregulation of muscle genes at the myoblast stage while at later stages nearly 50 % of the 5AC-treated myotubes displayed a mature, well-defined sarcomere organization as well as spontaneous contractions that coincided with action potentials and intracellular calcium transients. Both the percentage of striated myotubes and their contractile activity could be inhibited by 20 nM TTX, 10 M ryanodine and 100 M nifedipine, suggesting that action potential-induced calcium transients are responsible for these characteristics. Our data suggest that genomic demethylation induced by 5AC overcomes an epigenetic barrier that prevents untreated C2C12 myotubes from reaching full maturity.
Publication Title
Epigenetics: DNA demethylation promotes skeletal myotube maturation.
Sample Metadata Fields
Cell line, Treatment
View Samples- Mus musculus
- 30 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Background: MicroRNAs (miRNAs) are a family of small, non-coding single-stranded RNA molecules involved in post-transcriptional regulation of gene expression. As such, they are believed to play a role in regulating the step-wise changes in gene expression patterns that occur during cell fate specification of multipotent stem cells. Here, we have studied whether terminal differentiation of C2C12 myoblasts is indeed controlled by lineage-specific changes in miRNA expression.
Publication Title
MicroRNA miR-378 promotes BMP2-induced osteogenic differentiation of mesenchymal progenitor cells.
Sample Metadata Fields
Cell line
View Samples- Mus musculus
- 5 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Although the effects of thyroid hormones (TH) on the brain development have been extensively studied perinatally, effects of TH of maternal origin on the fetal brain development have been largely unexplored. We applied a high throughput study on the mouse models with aberrant TH levels on gestation day (GD) 16, before the onset of fetal thyroid function. Although 3 day treatment with methimazole (MMI) and perchlorate significantly decreased TH levels in fetal cerebral cortex, few changes in the abundance of mRNA were revealed by the microarray analysis. Injection TH to dams 12 hours before sacrifice on GD 16 induced 161 genes significantly changed in fetal cortex. Nine out of 10 selected genes were confirmed with RT-PCR, including known TH responsive gene Klf9 and other novel TH responsive genes such as Appbp2, Ppap2b and Fgfr1op2. TH regulation of the expression of these genes was also confirmed with cultured N2a cells. Thyroid responsive elements (TREs) in the promoters of these genes were identified using electrophoresis mobility shift assay. TH effect on microRNA (miRNA) expression in developing cortex on GD 16 and postnatal day (PND) 15 was investigated with microarray and RT-PCR. Some of miRNAs and precursors decreased in fetal cortex from the dams injected with TH on GD 16, including miR-16 and miR-106. Using 3 untranslate region reporter vector, we identified Klf9 is one of the target genes of miR-106, while Ppap2b is the target of miR-16. These results indicated that TH regulation on gene expression could through TR-TRE interaction and through regulating target miRNA expression. This study is the first report to identify TH responsive genes and miRNAs genome wide in the early fetal brain; it provides evidence to further understand the mechanism of TH effect on brain development.
Publication Title
Transient Maternal Hypothyroxinemia Potentiates the Transcriptional Response to Exogenous Thyroid Hormone in the Fetal Cerebral Cortex Before the Onset of Fetal Thyroid Function: A Messenger and MicroRNA Profiling Study.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Homo sapiens
- 69 Downloadable Samples
- Affymetrix Human Gene 1.1 ST Array (hugene11st)
Description
The gut microbiota has been implicated in obesity and cardiometabolic diseases, although evidence in humans is scarce. We investigated how gut microbiota manipulation by antibiotics (7-day administration of amoxicillin, vancomycin, or placebo) affects host metabolism in 57 obese, prediabetic men. Vancomycin, but not amoxicillin, decreased bacterial diversity and reduced Firmicutes involved in short-chain fatty acid and bile acid metabolism, concomitant with altered plasma and/or fecal metabolite concentrations. Adipose tissue gene expression of oxidative pathways was upregulated by antibiotics, whereas immune-related pathways were downregulated by vancomycin. Antibiotics did not affect tissue-specific insulin sensitivity, energy/substrate metabolism, postprandial hormones and metabolites, systemic inflammation, gut permeability, and adipocyte size. Importantly, energy harvest, adipocyte size, and whole-body insulin sensitivity were not altered at 8-week follow-up, despite a still considerably altered microbial composition, indicating that interference with adult microbiota by 7-day antibiotic treatment has no clinically relevant impact on metabolic health in obese humans.
Publication Title
Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans: A Randomized Double-Blind Placebo-Controlled Trial.
Sample Metadata Fields
Sex, Specimen part, Disease, Disease stage, Treatment, Subject, Time
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina HiSeq 2500
Description
Immunoglobulin A (IgA) is the major secretory immunoglobulin isotype at mucosal surfaces where it regulates microbial commensalism and excludes luminal factors from contacting intestinal epithelial cells (IEC). IEC endoplasmic reticulum (ER) stress induces a polyreactive IgA response which protects from small intestinal inflammation. IEC ER stress causes expansion and activation of peritoneal B1b cells independent of microbiota and T cells that culminates in increased lamina propria and luminal IgA. Xbp1dIEC mice exhibit IEC ER stress by conditional deletion of X-box-binding protein 1 (XBP1). Here we examine single-cell transcriptomes of peritoneal cavity cells of germ-free Xbp1dIEC mice (KO) compared to littermate controls (WT). Overall design: Single-cell gene expression profiles of peritoneal cavity cells of 10-week-old germ-free Xbp1dIEC and WT mice were generated using a droplet-based system (10X Genomics Chromium).
Publication Title
Epithelial endoplasmic reticulum stress orchestrates a protective IgA response.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Genome 430A 2.0 Array (mouse430a2)
Description
Foxp3+ T-regulatory cells (Tregs) are key to immune homeostasis such that their diminished numbers or function can cause autoimmunity and allograft rejection. Foxp3+ Tregs express histone/protein deacetylases (HDACs) that regulate chromatin remodeling, gene expression and protein function. Pan-HDAC inhibitors developed for oncology enhance Treg production and suppression but have limited non-oncologic applications given their broad effects. We show, using HDAC6-deficient mice and WT mice treated with HDAC6-specific inhibitors, that HDAC6 inhibition promotes Treg suppressive activity in models of inflammation and autoimmunity, including multiple forms of experimental colitis and fully MHC-incompatible cardiac allograft rejection. Many of the beneficial effects of HDAC6 targeting are also achieved by inhibition of the HDAC6-regulated protein, HSP90. Hence, selective targeting of a single HDAC isoform, HDAC6, or its downstream target, HSP90, can promote Treg-dependent suppression of autoimmunity and transplant rejection.
Publication Title
Histone deacetylase 6 and heat shock protein 90 control the functions of Foxp3(+) T-regulatory cells.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 24 Downloadable Samples
Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Antiviral Protection via RdRP-Mediated Stable Activation of Innate Immunity.
Sample Metadata Fields
Sex, Specimen part
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Previously, we reported that mice made transgenic for a picornaviral RdRP the 3Dpol protein of Theilers murine encephalomyelitis virus (TMEV) suppress infection by diverse viral families. How the picornaviral RdRP transgene exerted antiviral protection in vivo was not known. To investigate the molecular mechanism, we determined gene expression profiles in spinal cords of WT and RdRP transgenic mice prior to (baseline) and after (2 days) infection with Encephalomyocarditis Virus (EMCV).
Publication Title
Antiviral Protection via RdRP-Mediated Stable Activation of Innate Immunity.
Sample Metadata Fields
Sex
View Samples- Homo sapiens
- 4 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Previously, we reported that mice made transgenic for a picornaviral RdRP the 3Dpol protein of Theilers murine encephalomyelitis virus (TMEV) suppress infection by diverse viruses. Using mouse genetic studies, we determined that uninfected RdRP transgenic mice inherently induce an arsenel of prominent antiviral effectors and that this phenotype is MDA5-, MAVS- and IFNR-dependent. To determine the mechanism underlying MDA5 activation and induction of constitutive antiviral signaling by the picornaviral RdRP, we constructed mutant RdRP transgenes. First, we introduced pervasive, coding-neutral point mutations into the RdRP cDNA to maximally disrupt primary and secondary RNA structure (RdRPrna). Another mutant, RdRPcat, lacks catalytic activity due to alanine substitution of the key catalytic center triad aspartate residues (D233, D328, and D329), but is otherwise intact at the nucleotide and amino acid levels. The WT, RdRPrna, and RdRPcat versions of the RdRP transgenes were transduced with lentiviral vectors into human THP-1 monocytes, with RdRP mRNA transcription controlled by the Spleen Focus Forming Virus (SFFV) promoter. In parallel a control cell line transduced with a vector lacking any RdRP transgene (null THP-1) was generated.
Publication Title
Antiviral Protection via RdRP-Mediated Stable Activation of Innate Immunity.
Sample Metadata Fields
Specimen part
View Samples