Antiproliferative effects and mechanisms of liver X receptor ligands in pancreatic ductal adenocarcinoma cells
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ABSTRACT: This microarray is an analysis of differentially expressed genes in three pancreatic ductal adenocarcinoma cell lines treated with LXR-agonist GW 3965. We first report that GW 3965 has antiproliferative effects in three PDAC cell lines. This microarray was designed to identify key mechanisms of the antiproliferative effect of LXR agonists within pancreatic cancer cell lines. Total RNA obtained from BxPC-3, MIA-PaCa-2, and PANC-1 pancreatic cancer cells grown in culture treated GW 3965 or ethanol (vehicle control) for 72 hours.
Project description:Analysis of differentially expressed genes in response to the LXR agonist GW3965 in the MCF-7, T-47D, SK-BR-3, and MDA-MB-231 breast cancer cell lines. It was previously reported that GW3965 has antiproliferative effects on these 4 different breast cancer cell lines. In the present study, we additionally determine the effects of the LXR ligand on breast cancer cells and determine their mechanism of action in reducing cell proliferation. Total RNA obtained from 4 different breast cancer cell lines (MCF-7, T-47D, SK-BR-3, MDA-MB-231) grown in culture treated with ethanol (control) or GW3965 (GW-treated, experimental) for 48 hours. Triplicates were performed.
Project description:Analysis of change in transcriptional networking and disection of the TRalpha and TRbeta roles in hADSC, and during differentiation of hADSC towadrd different lineages. Total RNA was obtained from hADSC, and adipocytes, chondrocytes and osteoblasts differentiated from hADSC treated with triiodothytonine (T3) for 0 and 18 h. T3 response in each cell line was analyzed.
Project description:Synthetic selective thyroid hormone (TH) receptor (TR) modulators (STRMs) exhibit beneficial effects on dyslipidemias in animals and humans and reduce obesity, fatty liver and insulin resistance in preclinical animal models. STRMs differ from native THs in preferential binding to the TR? subtype versus TR?, increased uptake into liver and reduced uptake into other tissues. However, selective modulators of other nuclear receptors (NRs) exhibit important gene-selective actions which have been attributed to differential effects on receptor conformation and dynamics and these effects can have profound influences in animals and humans. While there are suggestions that STRMs could exhibit such gene-specific actions, the extent to which these effects are actually observed in vivo has not been explored. Here, we show that saturating concentrations of the main active form of TH, triiodothyronine (T3), and the prototype STRM GC-1 induce identical gene-sets in livers of euthyroid and hypothyroid mice and a human cultured hepatoma cell line that only expresses TR?, HepG2. We find one case in which GC-1 exhibits a modest gene-specific reduction in potency versus T3, at angiopoietin-like factor 4 (ANGPTL4) in HepG2. Investigation of the latter effect confirms that GC-1 acts through TR? to directly induce this gene. However, this gene-selective GC-1 activity is not related to unusual T3 response element (TRE) sequence, unlike previously documented promoter-selective STRM actions. Together, our data suggest that T3 and GC-1 exhibit almost identical gene regulation properties and that gene-selective actions of GC-1 and similar STRMs will be subtle and rare. We treated 9-week old euthyroid male C57/Bl6 mice with vehicle or ligand (T3 or GC-1) by a single oral gavage (n=5 per treatment) and also performed a similar study in which mice were first made hypothyroid by two week feeding on iodine deficient diet (n=3-4 per treatment), analyzing mRNA 24h post treatment [Illumina]. We also treated HepG2 with vehicle or 10nM ligand (T3 or GC1; n=3 / treatment), analyzing mRNA 24h post treatment [Affymetrix].
Project description:Wandering third instar larvae were dissected where the eye disc was separated from the antenna and brain using WT and Rbf mutants. The tissues were dissociated into single cells and captured using Drop-seq. Single cell libraries were then generated from each cell and finally sequenced.
Project description:Polycomb group (PcG) proteins are required for normal differentiation and development, and their activity is found deregulated in cancer. PcG proteins are involved in gene silencing, however, whether they initiate or maintain transcriptional repression is a subject of debate. Here, we show that knockout of the Polycomb repressive complex 2 (PRC2) does not lead to significant gene expression changes in mouse embryonic stem cells (mESCs), and that it is dispensable for initiating silencing of target genes during differentiation. Transcriptional inhibition in mESCs is sufficient to induce genome-wide ectopic PRC2 recruitment to endogenous PcG target genes found in other tissues. PRC2 binding analysis shows that it is restricted to nucleosome-free CpG islands (CGIs) of un-transcribed genes. Our results show that it is the transcriptional state that governs PRC2 binding, and we propose that it binds by default to non-transcribed CGI genes to maintain their silenced state and to protect cell identity. RNA-seq time-course experiments during in vitro differentiation (0h, 24h, 48h and 72h) of Mus musculus wild-type E14 and Suz12 knock-out Embryonic Stem Cells with two biological replicates per condition.
Project description:Single-cell transcriptomic analysis to delineate key regulators of neurogenic commitment in the enteric nervous system. To resolve the molecular profiles of ENCCs and identify transcriptional signatures of lineage restriction and differentiation, we analyzed their transcriptomes by single-cell RNA-sequencing (scRNA-seq). E12.0 Sox10::CreERT2;Rosa26tdTomato (SER93|tdT) embryos were exposed to a single dose of TM (100g/g of dam body weight) and tdT+ gut cells were isolated 20-24 hours later by flow cytometry.
Project description:This SuperSeries is composed of the following subset Series: GSE32443: Identical gene regulation patterns of triiodothyronine (T3) and selective thyroid hormone receptor modulator GC-1 [Affymetrix] GSE32444: Identical gene regulation patterns of triiodothyronine (T3) and selective thyroid hormone receptor modulator GC-1 [Illumina] Refer to individual Series
Project description:Wandering third instar larvae were dissected where the eye disc was separated from the antenna and brain. The tissues were dissociated into single cells and captured using Drop-seq. Single cell libraries were then generated from each cell and finally sequenced.
Project description:G9a/GLP and Polycomb Repressive Complex 2 (PRC2) are two major epigenetic silencing machineries, which in particular methylate histone H3 on lysines 9 and 27 (H3K9 and H3K27), respectively. Although evidence of a crosstalk between H3K9 and H3K27 methylations has started to emerge, their actual interplay remains elusive. Here, we show that PRC2 and G9a/GLP interact physically and functionally. Moreover, combining different genome-wide approaches, we demonstrate that Ezh2 and G9a/GLP share an important number of common genomic targets, encoding developmental and neuronal regulators. Furthermore, we show that G9a enzymatic activity modulates PRC2 genomic recruitment to a subset of its target genes. Taken together, our findings demonstrate an unanticipated interplay between two main histone lysine methylation mechanisms, which cooperate to maintain silencing of a subset of developmental genes. RNA-seq has been perform in triplicate on mES cell (TT2 : Wildtype, and KO G9a-/-)
Project description:Analysis of the extent to which inter-individual variation in mRNA decay contributes to inter-individual variation in gene expression levels in humans. The study examines properties of genome-wide decay rates and the relationship between mRNA decay and gene expression across genes, across individuals, and finally across genotype classes. 70 human lymphoblastoid cell lines were treated with Actinomycin D to arrest transcription. Transcript abundance was measured at 5 timepoints: before transcription (0 hours) and after transcription (0.5 hours, 1 hour, 2 hours, and 4 hours). Data was then used to estimate gene-specific decay rates genome-wide.