The discovery of genetic variants in the CHRNA5-CHRNA3-CHRNB4 gene cluster associated with heavy smoking and higher relapse risk has led to the identification of the midbrain habenula- interpeduncular axis as a critical relay circuit in the control of nicotine addiction
Reexposure to nicotine during withdrawal increases the pacemaking activity of cholinergic habenular neurons.
Specimen part, DiseaseView Samples
Current pharmacotherapies for symptomatic benign prostatic hyperplasia (BPH), an androgen receptor (AR) driven, inflammatory disorder affecting elderly men, include 5a-reductase (5AR) inhibitors (i.e. dutasteride and finasteride) to block the conversion of testosterone to the more potent AR ligand dihydrotestosterone (DHT). Since DHT is the precursor for estrogen receptor ß (ERß) ligands, 5AR inhibitors could potentially limit ERß activation, which maintains prostate tissue homeostasis. We have uncovered signaling pathways in BPH-derived prostate epithelial cells (BPH-1) that are impacted by 5AR inhibition. The induction of apoptosis and repression of the cell-adhesion protein E-cadherin by the 5AR inhibitor, dutasteride, requires both ERß and TGFß. Dutasteride also induces cyclooxygenase type 2 (COX-2), which functions in a negative-feedback loop in TGFß and ERß signaling pathways as evidenced by the potentiation of apoptosis induced by dutasteride or finasteride upon pharmacological inhibition or shRNA-mediated ablation of COX-2. Concurrently, COX-2 positively impacts ERß action through its effect on the expression of a number of steroidogenic enzymes in the ERß-ligand metabolic pathway. Therefore, effective combination pharmacotherapies, which have included non-steroidal anti-inflammatory drugs, must take into account biochemical pathways affected by 5AR inhibition and opposing effects of COX-2 on the tissue protective action of ERß. Overall design: Next-generation sequencing (n=3) of shRNA mediated knockdown of COX-2 or scrambled control in BPH-1 prostate epithelial cell line
Opposing Effects of Cyclooxygenase-2 (COX-2) on Estrogen Receptor β (ERβ) Response to 5α-Reductase Inhibition in Prostate Epithelial Cells.
Specimen part, Cell line, SubjectView Samples
We used RNA-Seq to detail the global program of sexually dimorphic dexamethasone regulated gene expression in embryonic hypothalamic neural progenitor/stem cells. Overall design: RNAseq on Primary E14.5 mouse hyothalamic neurosphere cultures. 4 conditions - Male Dex, Male EtOH, Female Dex and Female EtOH. There are 3 biological replicates for each condition and all the 12 samples are run on two lanes (techinical duplicates).
Research Resource: The Dexamethasone Transcriptome in Hypothalamic Embryonic Neural Stem Cells.
Sex, Cell line, Treatment, SubjectView Samples
Gene expression profiling of macrophages derived from WT and Vdr deficient mice after stimulation with IFNgamma and/or 1alpha,25(OH)2D3
1alpha,25-Dihydroxyvitamin D3 is a potent suppressor of interferon gamma-mediated macrophage activation.
No sample metadata fieldsView Samples
The quality of maternal care in early-life plays a crucial role in mammalian neurodevelopment. Augmented maternal care (AMC) is a well-established rodent model of enhanced neonatal care. Rats that have undergone AMC have improved stress resilience and cognition compared with rats that have experienced normal levels of maternal care or adverse neonatal stress. However, the epigenomic basis of long-lived responses to AMC has not been previously explored. Thus, we employed whole-genome bisulfite sequencing (WGBS), RNA-sequencing (RNA-seq), and a multiplex microRNA (miRNA) assay to assess DNA cytosine methylation, gene expression, and miRNA expression, respectively. The integrated results identify a suite of 20 prioritized candidates impacted by AMC. Overall, these results identified AMC-induced regulatory differences in genes related to neurotransmission, neurodevelopment, protein synthesis, and oxidative phosphorylation in addition to the expected stress response genes. Together, these unbiased results represent a key progression in understanding the complex mechanisms underlying the early-life mechanisms for AMC programming stress resiliency. Overall design: DNA methylation and RNA were assayed in augmented maternal care male rats as well as controls.
Experience-dependent neuroplasticity of the developing hypothalamus: integrative epigenomic approaches.
Sex, Specimen part, Treatment, SubjectView Samples
Analysis of the transcriptome of mononuclear side population (SP) and main population (MP) cells of human fetal skeletal muscle from 12 human subjects of gestational age 14-18 weeks.
Regulation of myogenic progenitor proliferation in human fetal skeletal muscle by BMP4 and its antagonist Gremlin.
Specimen partView Samples
Functional analysis of ABCB5 in A375 and G3361 melanoma cells, by comparing stably-transfected controls to ABCB5-shRNA-targeted cells.
ABCB5 maintains melanoma-initiating cells through a proinflammatory cytokine signaling circuit.
Specimen part, Cell lineView Samples
To find BMAL1-regulated genes in mice pituitary gland we performed a differential microarray from wild-type vs Bmal1-/- knock-out mice
Chromatin remodeling as a mechanism for circadian prolactin transcription: rhythmic NONO and SFPQ recruitment to HLTF.
Sex, Specimen partView Samples
Worms were treated with bcat-1 RNAi Jena Centre for Systems Biology of Ageing - JenAge (www.jenage.de) Overall design: 6 samples: 3 replicates for bcat-1 RNAi treatment; 3 replicates for controls
Branched-chain amino acid catabolism is a conserved regulator of physiological ageing.
Cell line, SubjectView Samples
Glucocorticoids remain the most widely used class of anti-inflammatory and immunosuppressive agents. They act primarily by binding to the glucocorticoid receptor, resulting in direct and indirect effects on gene expression. The current understanding of glucocorticoid effects on transcription in human cells is based mostly on studies of cancer cell lines, immortalized cell lines, or highly mixed populations of primary cells (such as peripheral blood mononuclear cells). To advance the understanding of the transcriptome-wide effects of glucocorticoids on highly pure populations of primary human cells, we performed RNA-seq on nine such cell populations at two time points after in vitro exposure to methylprednisolone or vehicle. Overall design: Nine cell types were studied: four hematopoietic (circulating B cells, CD4+ T cells, monocytes, and neutrophils) and five non-hematopoietic (endothelial cells, fibroblasts, myoblasts, osteoblasts, and preadipocytes). Each cell type was obtained from a separate cohort of 4 unrelated healthy human donors (4 biological replicates per cell type: BR1 - BR4). Cells form each donor were independently cultured and exposed in vitro to glucocorticoid or vehicle. Non-hematopoietic cells were incubated until the early plateau phase of growth, then exposed to methylprednisolone or vehicle. Hematopoietic cells were collected from peripheral blood, purified by magnetic selection (negative selection for B cells, CD4+ T cells and neutrophils; positive selection for monocytes). Purified B cells, CD4+ T cells, and monocytes were incubated overnight, then exposed to methylprednisolone or vehicle. Purified neutrophils were cultured for 4 hours, then exposed to methylprednisolone or vehicle. Ethanol was used as a vehicle for methylprednisolone. Estimated final concentrations were 8500 mcg/L (22.7 mcM) for methylprednisolone and 0.07% (15.57 mM) for ethanol (vehicle). For each cell type, samples were collected at two time points after treatment with methylprednisolone or vehicle: 2 hours and 6 hours. Samples were collected into TRIzol reagent and frozen at -80Â°C prior to RNA extraction. RNA-seq data for all samples is made available in this GEO Series.
Immune regulation by glucocorticoids can be linked to cell type-dependent transcriptional responses.
Specimen part, Subject, TimeView Samples