Study of the short term (within the first 330 seconds) transcriptional response of S.cerevisiae upon a sudden addition of glucose.
When transcriptome meets metabolome: fast cellular responses of yeast to sudden relief of glucose limitation.
No sample metadata fields
View SamplesConjugates of fatty acids and amines, including endocannabinoids, are known to play important roles as endogenous signalling molecules. Among these, the ethanolamine conjugate of the n-3 poly unsaturated long chain fatty acid (PUFA) docosahexaenoic acid (22:6n-3) (DHA) was shown to possess strong anti-inflammatory properties.
Docosahexaenoyl serotonin, an endogenously formed n-3 fatty acid-serotonin conjugate has anti-inflammatory properties by attenuating IL-23-IL-17 signaling in macrophages.
Treatment
View SamplesThe transcriptional regulator EVI1 has an essential role in early hematopoiesis and development. However, aberrantly high expression of EVI1 has potent oncogenic properties and confers poor prognosis and chemo-resistance in leukemia and solid tumors. To investigate to what extent EVI1 function might be regulated by posttranslational modifications, we carried out mass spectrometry- and antibody-based analyses and uncovered an ATM-mediated double phosphorylation of EVI1 at the carboxy-terminal S858/S860 SQS motif. In the presence of genotoxic stress, EVI1-WT (SQS), but not site mutated EVI1-AQA was able to maintain transcriptional patterns and transformation potency, while under standard conditions carboxy-terminal mutation had no effect. Maintenance of hematopoietic progenitor cell clonogenic potential was profoundly impaired with EVI1-AQA compared with EVI1-WT, in particular in the presence of genotoxic stress. Exploring mechanistic events underlying these observations, we showed that after genotoxic stress EVI1-WT, but not EVI1-AQA increased its level of association with its functionally essential interaction partner CtBP1, implying a role for ATM in regulating EVI1 protein interactions via phosphorylation. This aspect of EVI1 regulation is therapeutically relevant, as chemotherapy-induced genotoxicity might detrimentally sustain EVI1 function via stress response mediated phosphorylation, and ATM-inhibition might be of specific targeted benefit in EVI1-overexpressing malignancies. Overall design: Poly-A RNA sequencing (RNAseq) analysis of EVI1-mediated modulation of gene expression RNA was extracted from HEK293 cells, which were subjected to transient transfection using half confluent cultures with pCMV-flag, pCMV-EVI1-WT-flag or pCMV-EVI1-AQA-flag, exposed to 150 µM H2O2 or left untreated for 8 h.
EVI1 carboxy-terminal phosphorylation is ATM-mediated and sustains transcriptional modulation and self-renewal via enhanced CtBP1 association.
Cell line, Treatment, Subject
View SamplesThe goal of this study was to determine how decreased mitochondrial citrate export influences gene expression in Drosophila larvae. RNA was isolated from Drosopohila sea mutants, which exhibiti decreased mitochondrial citrate transport activity, and a genetically-matched control strain during mid-L3 development. Overall design: Larvae were collected as described in Li, H., Tennessen, J. M. Preparation of Drosophila Larval Samples for Gas Chromatography-Mass Spectrometry (GC-MS)-based Metabolomics. J. Vis. Exp. (136), e57847, doi:10.3791/57847 (2018). RNA was purified from staged mid-L3 larvae using a RNeasy Mini Kit (Qiagen). Sequencing was performed using an Illumina NextSeq500 platform with 75 bp sequencing module generating 41 bp paired-end reads. After the sequencing run, demultiplexing was performed with bcl2fastq v2.20.0.422.
A <i>Drosophila</i> model of combined D-2- and L-2-hydroxyglutaric aciduria reveals a mechanism linking mitochondrial citrate export with oncometabolite accumulation.
Subject
View SamplesCancer cells utilize a unique form of aerobic glycolysis, called the Warburg effect, to efficiently produce the macromolecules required for proliferation. Here we show that a metabolic program related to the Warburg effect is used during normal Drosophila development and regulated by the fly ortholog of the Estrogen-Related Receptor (ERR) family of nuclear receptors. dERR null mutants die as second instar larvae with abnormally low ATP levels, diminished triacylglyceride stores, and elevated levels of circulating sugars. Metabolomic profiling revealed that the pathways affected in these mutants correspond to those used in the Warburg effect. The expression of active dERR protein in mid-embryogenesis triggers a coordinate switch in gene expression that drives a metabolic program supporting the dramatic growth that occurs during larval development. This study suggests that mammalian ERR family members may promote cancer by directing a metabolic state that supports proliferation.
The Drosophila estrogen-related receptor directs a metabolic switch that supports developmental growth.
Specimen part
View SamplesHigh-throughput sequencing of primary cutaneous follicle center lymphoma (PCFCL), primary cutaneous diffuse large B-cell lymphoma, leg type (PCLBCL-LT) and in vitro activated peripheral blood B-cells. We performed high-throughput sequencing analysis on frozen tumor biopsies from 19 cases of PCFCL and PCLBCL-LT to establish microRNA profiles. Cluster analysis of the complete microRNome could not distinguish between the two subtypes, but 16 single microRNAs were found to be differentially expressed. Overall design: Lymphoma miRNA profiles of were generated by deep sequencing, using Illumina Genome Analyzer II.
MicroRNA profiling of primary cutaneous large B-cell lymphomas.
No sample metadata fields
View SamplesLow reduced red:far-red ratio [R:FR] signaling through phytochromes induces shade avoidance responses, including petiole elongation. Jasmonic acid-mediated defense against herbivores and pathogens is inhibited under these conditions.
Low red/far-red ratios reduce Arabidopsis resistance to Botrytis cinerea and jasmonate responses via a COI1-JAZ10-dependent, salicylic acid-independent mechanism.
Specimen part, Treatment
View SamplesHere we studied the effects of anticonvulsant drug exposure in a human embryonic stem cell (hESC) based neuro- developmental toxicity test (hESTn). During neural differentiation the cells were exposed, for either 1 or 7 days, to non-cytotoxic concentration ranges of valproic acid (VPA) or carbamazepine (CBZ), anti-epileptic drugs known to cause neurodevelopmental toxicity.
Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay.
Time
View SamplesLow R:FR signaling through phytochromes induces shade avoidance responses, including petiole elongation. Salicylic acid-mediated defense against pathogens is inhibited under these conditions.
Perception of low red:far-red ratio compromises both salicylic acid- and jasmonic acid-dependent pathogen defences in Arabidopsis.
Age, Specimen part, Treatment
View SamplesPlants have evolved shoot elongation mechanisms to escape from diverse environmental stresses such as flooding and vegetative shade. The apparent similarity in growth responses suggests possible convergence of the signalling pathways. Shoot elongation is mediated by passive ethylene accumulating in flooded plant organs and by changes in light quality and quantity under vegetation shade. Here we study hypocotyl elongation as a proxy for shoot elongation and delineated Arabidopsis hypocotyl length kinetics in response to ethylene and shade. Based on these kinetics, we further investigated ethylene and shade-induced genome-wide gene expression changes in hypocotyls and cotyledons separately. Both treatments induced a more extensive transcriptome reconfiguration in the hypocotyls compared to the cotyledons. Bioinformatics analyses suggested contrasting regulation of growth promotion- and photosynthesis-related genes. These analyses also suggested an induction of auxin, brassinosteroid and gibberellin signatures and the involvement of several candidate regulators in the elongating hypocotyls. Pharmacological and mutant analyses confirmed the functional involvement of several of these candidate genes and physiological control points in regulating stress-escape responses to different environmental stimuli. We discuss how these signaling networks might be integrated and conclude that plants, when facing different stresses, utilise a conserved set of transcriptionally regulated genes to modulate and fine tune growth.
Ethylene- and Shade-Induced Hypocotyl Elongation Share Transcriptome Patterns and Functional Regulators.
Specimen part, Treatment, Time
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