In order to identify transcript changes in response to DEF , we used human macrophages with or without DEF treatment. In order to study the effect of iron chelation on LPS-polarized macrophage transcriptome, we exposed DEF-treated or control macrophages to short time exposure to LPS. We then performed whole-genome transcriptome sequencing by RNA-sequencing (RNA-seq). Overall design: Macrophages from 3 healthy donors were either treated with DEF (500 µM - designated as DEF) or left unstimulated (CONTROL). LPS treatment (100 ng/ml, 3 hours) was performed in cells with DEF (designated as LPS+DEF) or without (LPS). RNA-seq was performed on Illumina Hiseq 2500
Acute Iron Deprivation Reprograms Human Macrophage Metabolism and Reduces Inflammation In Vivo.
Specimen part, Treatment, Subject
View SamplesSox3 has been shown to be expressed within neural progenitors of the developing mouse central nervous system. However, identification of Sox3 targets within neural progenitors has remained elusive.
Dbx1 is a direct target of SOX3 in the spinal cord.
Specimen part, Cell line
View SamplesAE-expressing murine BM cells treated with all-trans retinoic acid (ATRA) in semi-solid methycellulose-based cultures show an increase in self-renewal capacity whilst treatment with a specific RARa agonist NRX195183 reduces their clonogenicity. Gene expression analysis was performed to further investigate the molecular mechanisms underlying these observations. Upregulated gene sets were identified in the ATRA-treated AE BM cells.
ATRA and the specific RARα agonist, NRX195183, have opposing effects on the clonogenicity of pre-leukemic murine AML1-ETO bone marrow cells.
Specimen part, Treatment
View SamplesPurpose: To identify novel genes regulated by the aryl hydrocarbon receptor that influence human Th17 cell function. Methods: Naïve CD4 T cells from peripheral blood of six healthy human volunteers were cultured under four experimental conditions for three days: anti-CD3 and anti-CD28 antibodies (Media control), Media with Th17 conditions (IL-6, TGF-b, IL-1b, IL-23), Th17+FICZ and Th17+CH223191. Total RNA was extracted from each sample on day 3 and sequenced in a paired-end 2x50bp strategy on an Illumina HiSeq1500. A total of six donors were analyzed. Results: AhR activation with FICZ suppressed IL-17 production from human CD4 T cells and increased IL-22. AhR inhibition with CH223191 potently suppressed IL-22 and modestly increased IL-17 production. On day 3, the number of significantly regulated genes for each treatment were 975 (Th17), 88 (Th17+FICZ) and 142 (Th17+CH223191). 11 common genes were significantly regulated by all three treatments. One of these, GPR68, was investigated further in functional studies since its expression correlated with IL-22 production. Activation of GPR68 with a positive allosteric modulator suppressed IL-22 concentrations in human Th17 cell cultures. Conclusions: Our study demonstrates that GPR68 activation can negatively regulate IL-22 production from human CD4 T cells in the presence of an AhR agonist. RNA-seq is a powerful method to identify novel gene targets that regulate cytokines involved in chronic inflammatory diseases. Overall design: Naïve CD4 T cells were purified from peripheral blood mononuclear cells isolated from six patient samples. Four experimental conditions were created for each sample: media only (control); Th17 differentiated; Th17+FICZ; and Th17+CH223191. Total RNA was extracted from each sample on day 3 and sequenced in a paired-end 2x50bp strategy on an Illumina HiSeq1500. Differential gene expression analysis identified genes that were expressed at significantly different levels than the control (Media). Ingenuity pathway analysis revealed the most common cellular functions for genes regulated by each treatment.
Cytokine Regulation in Human CD4 T Cells by the Aryl Hydrocarbon Receptor and Gq-Coupled Receptors.
Specimen part, Treatment, Subject
View SamplesDU145 prostate cancer cells were treated with 50 ng/ml FGF19 and 50 ug/ml heparin, or 10 ng/ml TNFalpha, or both
The receptor tyrosine kinase FGFR4 negatively regulates NF-kappaB signaling.
Cell line
View SamplesPrimary glioblastoma (GBM) cultures vary with respect to differentiation competency. We sought to identify putative transcription factors necessary for the differentiation of GBM cultures. In this dataset, we include expression data obtained from 2 human-fetal neural stem cell (HF-NS) cultures and 2 GBM stem cell (GSC) cultures. We assessed changes in gene expression from 3 timepoints during an in vitro differentiation protocol.
ASCL1 Reorganizes Chromatin to Direct Neuronal Fate and Suppress Tumorigenicity of Glioblastoma Stem Cells.
Specimen part, Time
View SamplesPolycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder that affects 5-10% of reproductive aged women. The hallmark characteristic of PCOS is increased ovarian androgen synthesis. Previous studies by our laboratory demonstrated that increased androgen synthesis is a stable biochemical phenotype of PCOS theca cells which are the primary source of ovarian androgen production. The increase in theca cell steroidogenesis was due to an increase in expression of several steroidogenic enzymes including CYP17 and CYP11A but not StAR. Interestingly, the anti-epileptic drug valproic acid induces increased theca cell androgen synthesis and increased CYP17 and CYP11A mRNA levels. In this study we have characterized the gene expression profiles of theca cells obtained from normal or polycystic ovaries which were maintained in the absence (UNT) or presence (VPA) of valproic acid. The data identifed new candidate genes and novel signaling pathways which may contribute to the manifestation of PCOS phenotypes including increased androgen production. The experiments in this study were carried using the Affymetrix U133A and U133B oligonucleotide chips.
Valproate-induced alterations in human theca cell gene expression: clues to the association between valproate use and metabolic side effects.
No sample metadata fields
View SamplesPrimary glioma stem cells cultured as neurospheres in NBL media with growth factors were subjected to treatment with the non-toxic, non-psychoactive cannabis compound
Reactive oxygen species-mediated therapeutic response and resistance in glioblastoma.
Specimen part, Disease stage
View SamplesWe explored the effects of dexamethasone and lenalidomide, individually and in combination, on the differentiation of primary human bone marrow progenitor cells in vitro. Both agents promote erythropoiesis, increasing the absolute number of erythroid cells produced from normal CD34+ cells and from CD34+ cells with the types of ribosome dysfunction found in DBA and del(5q) MDS. However, the drugs had distinct effects on the production of erythroid progenitor colonies; dexamethasone selectively increased the number burst-forming units-erythroid (BFU-E), while lenalidomide specifically increased colony-forming units-erythroid (CFU-E). Use of the drugs in combination demonstrates that their effects are not redundant.
Dexamethasone and lenalidomide have distinct functional effects on erythropoiesis.
Specimen part, Treatment
View SamplesSca1+/cKit hematopoietic BMCs of hosts bearing primary tumors promote the growth of distant tumors that form with a myofibroblast-rich, desmoplastic stroma. BMCs from old mice bearing primary tumors lack this ability
Hematopoietic Age at Onset of Triple-Negative Breast Cancer Dictates Disease Aggressiveness and Progression.
Sex, Specimen part
View Samples