V600E being the most common mutation in BRAF, leads to constitutive activation of the MAPK signaling pathway. The majority of V600E BRAF positive melanoma patients treated with the BRAF inhibitor vemurafenib showed initial good clinical responses but relapsed due to acquired resistance to the drug. The aim of the present study was to identify possible biomarkers associated with the emergence of drug resistant melanoma cells. To this end we analyzed the differential gene expression of vemurafenib-sensitive and vemurafenib resistant brain and lung metastasizing melanoma cells.
Vemurafenib resistance selects for highly malignant brain and lung-metastasizing melanoma cells.
Specimen part, Treatment
View SamplesCbtOE (Tim-gal4; UAS-cbtFLAG), Tim-gal4 (control for CbtOE), cbtRNAi (Tim-gal4-UAS-Dcr2-UAS-cbtIR-cbtE1) and Tim-gal4;UAS-Dcr2 (control for CbtRNAi) flies. Flies were entrained in LD (light: dark) condition for 3-4 days and harvested at six time points: ZT3, ZT7, ZT11, ZT15, ZT19, ZT23 Fly heads were collected, RNA was extracted and RNA-seq libraries were prepared as previously described (Engreitz et al., 2013) Overall design: Three samples of cbtRNAi and three samples of their controls. Two samples of cbtOE with two samples of their controls.
The transcription factor Cabut coordinates energy metabolism and the circadian clock in response to sugar sensing.
Specimen part, Subject, Time
View SamplesControl (+/cbtE1-UAS-cbt RNAi) or cabut RNAi flies (Tim-gal4, UAS-cbt RNAi) were starved for 16 hours and then exposed to food containing different concentrations of sucrose: 0, 25, 50 and 100 % for 18 hours. Fly heads were collected, RNA was extracted and RNA-seq libraries were prepared as previously described (Engreitz et al., 2013) Overall design: For each sucrose concentration, two samples of cabut RNAi flies and one sample of control flies were sequenced.
The transcription factor Cabut coordinates energy metabolism and the circadian clock in response to sugar sensing.
Specimen part, Subject
View SamplesMicroarray data obtained from control, cbtRNAi (cabut RNAi), and cbtOE (cabut overexpression) flies. From each strain, fly heads at two different time points during the daynight cycle (ZT3 and ZT153) were collected.
The transcription factor Cabut coordinates energy metabolism and the circadian clock in response to sugar sensing.
Specimen part, Treatment
View SamplesViruses lack the basic machinery needed to replicate and therefore must hijack host metabolism to propagate. Virus-induced metabolic alterations have yet to be systematically studied in the context of the host transcriptional regulation, offering insight into host-pathogen metabolic interplay. In this work we identified Hepatitis C Virus (HCV)-responsive regulators by coupling system-wide metabolic flux analysis with targeted perturbation of nuclear receptors in primary human hepatocytes. We find HCV-induced up-regulation of glycolysis, ketogenesis and drug metabolism, controlled by activation of HNF4, PPAR, FXR and PXR, respectively. Pharmaceutical inhibition of HNF4 reversed HCV-induced glycolysis, blocking viral replication while increasing apoptosis in infected cells showing a viral-induced dependence on glycolysis. In contrast, pharmaceutical inhibition of PPAR or FXR reversed HCV-induced ketogenesis, but increased viral replication demonstrating a unique host anti-viral response. Our results show that viral-induced changes to host metabolism can be detrimental to its lifecycle demonstrating a distinct biological complexity.
Nuclear receptors control pro-viral and antiviral metabolic responses to hepatitis C virus infection.
Age, Specimen part
View SamplesTo understand the link between invasion behavior and the steps of metastasis formation, we isolated invasive subpopulations from MDA-MB-231 cells in vitro using matrigel coated boyden chambers. Whole genome transcriptional profiling was used to characterize the expression changes uniquely related to invasive abilities of these cells.
Invading basement membrane matrix is sufficient for MDA-MB-231 breast cancer cells to develop a stable in vivo metastatic phenotype.
Cell line
View SamplesTo screen for specific circadian outputs that may distinguish the pacemaker in the mammalian suprachiasmatic nucleus (SCN) from peripheral-type oscillators in which the canonical clockworks are similarly regulated in a circadian manner, the rhythmic behavior of the transcriptome in forskolin-stimulated NIH/3T3 fibroblasts was analyzed and compared to that found in the rat SCN in vivo and SCN2.2 cells in vitro. Similar to the scope of circadian gene expression in SCN2.2 cells and the rat SCN, NIH/3T3 fibroblasts exhibited circadian fluctuations in the expression of the core clock genes, Per2, Bmal1 (Mop3), and Cry1 and 323 functionally diverse transcripts (2.6%), many of which were involved in cell communication. Overlap in rhythmically-expressed transcripts among NIH/3T3 fibroblasts, SCN2.2 cells and the rat SCN was limited to these clock genes and four other genes that mediate fatty acid and lipid metabolism or function as nuclear factors. Compared to NIH/3T3 cells, circadian gene expression in SCN oscillators was more prevalent among cellular pathways mediating glucose metabolism and neurotransmission. Coupled with evidence for the rhythmic regulation of the inducible isoform of nitric oxide synthase, the enzyme responsible for the production of nitric oxide, in SCN2.2 cells and the rat SCN but not in fibroblasts, studies examining the effects of a NOS inhibitor on metabolic rhythms in co-cultures containing SCN2.2 cells and untreated NIH/3T3 cells suggest that this gaseous neurotransmitter may play a key role in SCN pacemaker function. Thus, this comparative analysis of circadian gene expression in SCN and non-SCN cells may have important implications in the selective identification of circadian signals involved in the coupling of SCN oscillators and the regulation of rhythmicity in downstream cells or tissues.
Circadian profiling of the transcriptome in NIH/3T3 fibroblasts: comparison with rhythmic gene expression in SCN2.2 cells and the rat SCN.
No sample metadata fields
View Samplesscreening of AtMYB44-responsive genes under 250mM NaCl treatment
Overexpression of AtMYB44 enhances stomatal closure to confer abiotic stress tolerance in transgenic Arabidopsis.
Compound
View SamplesAs exposure to episodic drought can impinge significantly on forest health and the establishment of productive tree plantations, there is great interest in understanding the mechanisms of drought response in trees. The ecologically dominant and economically important genus Populus, with its sequenced genome, provides an ideal opportunity to examine transcriptome level changes in trees in response to a drought stimulus. The transcriptome level drought response of two commercially important hybrid Populus clones (P. deltoides P. nigra, DN34, and P. nigra P. maximowiczii, NM6) was characterized over a diurnal period using a 4 2 2 completely randomized factorial ANOVA experimental design (four time points, two genotypes, and two treatment conditions) using Affymetrix Poplar GeneChip microarrays. Notably, the specific genes that exhibited changes in transcript abundance in response to drought differed between the genotypes and/or the time of day that they exhibited their greatest differences. This study emphasizes the fact that it is not possible to draw simple, generalized conclusions about the drought response of the genus Populus on the basis of one species, nor on the basis of results collected at a single time point. The data derived from our studies provide insights into the variety of genetic mechanisms underpinning the Populus drought response, and provide candidates for future experiments aimed at understanding this response across this economically and ecologically important genus.
Genotype and time of day shape the Populus drought response.
Age, Specimen part, Treatment
View SamplesThe capacity of embryonic stem cells to differentiate into all lineages of mature organism is precisely regulated by cellular signaling factors. STAT3 is a crucial transcription factor that plays a central role in maintaining embryonic stem cells identity. However the underlying mechanism how Stat3 directs differentiation is still not completely understood. Here we show that Stat3 positively regulates gene expression of methyltransferase like protein 8 (Mettl8) in mouse ES cells. We found that Mettl8 is dispensable for pluripotency but affects ESCs differentiation. Subsequently we discovered that Mettl8 interacts with Mapkbp1's mRNA, which is an intermediate factor in JNK signaling, and inhibits the translation of the mRNA. Thereby, Mettl8 prohibits the activation of JNK signaling and enhances the differentiation of mouse ESCs. Collectively, our study uncovers a Stat3 target Mettl8 which regulates mouse ESCs differentiation via JNK signaling. Overall design: mRNA profiles of E14 cells transfected with scramble siRNA or Mettl8 siRNA were generated by deep sequencing, in triplicate, using Illumina GAIIx.
The STAT3 Target Mettl8 Regulates Mouse ESC Differentiation via Inhibiting the JNK Pathway.
Specimen part, Cell line, Subject
View Samples