Glioblastoma multiforme is one of the most devastating cancers and presents unique challenges to therapy due to its aggressive behaviour. Cancer stem cells have been described to be the only cell population with tumorogenic capacity in glioblastoma. Therefore, effective therapeutic strategies targeting these cells may be beneficial. We have established different cultures of glioblastoma stem cells (GSCs) derived from surgical specimens and found that, after induction of differentiation, NFB was activated, which allows intermediate tumor precursor cells to remain cycling. We also showed that blockade of NFB signaling in differentiating GSCs by different genetic strategies or treatment with small molecule inhibitors, promoted replication arrest, progression to a mature phenotype, mainly neuronal cells, and senescence. This effect was partly mediated by downregulation of the NFB target gene cyclin D1. Furthermore, intravenous treatment of immunodeficient mice bearing human GSC-derived tumors with a novel small-molecule inhibitor of the NFB pathway induced senescence of tumor cells but no ultraestructural alterations of the brain parenchymal cells were detected. These findings reveal that activation of NFB may keep differentiating GSCs from acquiring a mature postmitotic phenotype, thus allowing cell proliferation, and support the rationale for therapeutic strategies aimed at promoting premature senescence in GSCs undergoing differentiation.
Blockade of the NFκB pathway drives differentiating glioblastoma-initiating cells into senescence both in vitro and in vivo.
Specimen part, Disease
View SamplesUV-B radiation affects leaf growth in a wide range of species. In this work, we demonstrate that UV-B levels present in solar radiation inhibits maize leaf growth without causing any other visible stress symptoms, including accumulation of DNA damage. We conducted kinematic analyses of cell division and expansion to understand the impact of UV-B radiation on these cellular processes. Our results demonstrate that the decrease in leaf growth is a consequence of a reduction in cell production, and a shortened growth zone (GZ) in UV-B irradiated leaves. To determine the molecular pathways involved in UV-B inhibition of leaf growth, we performed RNA sequencing on isolated GZ tissues of control and UV-B exposed plants. Our results show a link between the observed leaf growth inhibition and the expression of specific cell cycle and developmental genes, including Growth Regulating Factors (GRFs) and transcripts for proteins participating in different hormone pathways. Overall design: Factorial design with two factors: Treatment (control vs UV-B) x Zone I (0-1cm from base of the leaf), 2 (1-2cm from base of the leaf) and 3 (2-3cm from base of the leaf), 3 replicates
UV-B Inhibits Leaf Growth through Changes in Growth Regulating Factors and Gibberellin Levels.
Specimen part, Subject
View SamplesP1 encodes an R2R3-MYB transcription factor responsible for the accumulation of insecticidal flavones in maize silks and red phlobaphene pigments in pericarps and other floral tissues, which contributed to making P1 an important visual marker since the dawn of modern genetics. We conducted RNA-Seq using pericarps at two different stages, 14 and 25 days after pollination (DAP). High-throughput sequencing using the Illumina platform resulted in the generation of ~20 million high quality reads, from which ~90% aligned to the recently completed maize genome sequence corresponding to ~5 million reads for each one of the four samples. Overall design: Examination of two different RNA samples from two different stages of maize pericarp tissues.
A genome-wide regulatory framework identifies maize pericarp color1 controlled genes.
Specimen part, Subject
View SamplesP1 encodes an R2R3-MYB transcription factor responsible for the accumulation of insecticidal flavones in maize silks and red phlobaphene pigments in pericarps and other floral tissues, which contributed to making P1 an important visual marker since the dawn of modern genetics. We conducted RNA-Seq using from maize silks obtained at 2-3 days after emergence. High-throughput sequencing using the Illumina platform resulted in the generation of ~14 million high quality reads, corresponding to ~7 million reads for each sample, from which 76% aligned to the maize genome. Overall design: Examination of two different RNA samples from maize silks obtained at 2-3 days after emergence
A genome-wide regulatory framework identifies maize pericarp color1 controlled genes.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Osmotic stress induces phosphorylation of histone H3 at threonine 3 in pericentromeric regions of Arabidopsis thaliana.
Age, Specimen part
View SamplesHistone phosphorylation plays key roles in stress-induced transcriptional reprogramming in metazoans but its function(s) in land plants has remained relatively unexplored. Here we report that an Arabidopsis mutant defective in At3g03940 and At5g18190, encoding closely related Ser/Thr protein kinases, shows pleiotropic phenotypes including dwarfism and hypersensitivity to osmotic/salt stress. The double mutant has reduced global levels of phosphorylated histone H3 threonine 3 (H3T3ph), which are not enhanced, unlike the response in the wild type, by drought-like treatments. Genome-wide analyses revealed increased H3T3ph, slight enhancement in trimethylated histone H3 lysine 4 (H3K4me3), and a modest decrease in histone H3 occupancy in pericentromeric/knob regions of wild type plants under osmotic stress. However, despite these changes in heterochromatin, transposons and repeats remained largely transcriptionally repressed. In contrast, this reorganization of heterochromatin was mostly absent in the double mutant, which even under normal conditions exhibited lower H3T3ph levels in pericentromeric regions, and a few transposons and repeat sequences showed modest transcriptional activation. Interestingly, within actively transcribed protein-coding genes, H3T3ph density was minimal in 5 genic regions, coincidental with a peak of H3K4me3 accumulation. This pattern was not affected in the double mutant, implying the existence of additional H3T3 protein kinases in Arabidopsis. Our results suggest that At3g03940 and At5g18190 are involved in the phosphorylation of H3T3 in pericentromeric/knob regions and that this repressive epigenetic mark may be important for maintaining proper heterochromatic organization and, possibly, chromosome function(s).
Osmotic stress induces phosphorylation of histone H3 at threonine 3 in pericentromeric regions of Arabidopsis thaliana.
Age, Specimen part
View SamplesMurine pancreatic beta cell line MIN6 was growth at two different concentrations of glucose (22,2 and 5,5 mM of glucose), 37C, 5% CO2 and was treated at four different concentrations of human amylin (0, 1, 10 and 20 uM) during three different times (2, 12 and 24 hours)
Impairment of the ubiquitin-proteasome pathway is a downstream endoplasmic reticulum stress response induced by extracellular human islet amyloid polypeptide and contributes to pancreatic beta-cell apoptosis.
No sample metadata fields
View SamplesImpaired DNA replication is a hallmark of cancer and a cause of genomic instability. We report that, in addition to causing genetic change, impaired DNA replication during embryonic development can have major epigenetic consequences for a genome. In a genome-wide screen, we identified impaired DNA replication as causing increased expression from a repressed transgene in Caenorhabditis elegans. The acquired expression state behaved as an “epiallele,” being inherited for multiple generations before fully resetting. Derepression was not restricted to the transgene but was caused by a global reduction in heterochromatin-associated histone modifications due to the impaired retention of modified histones on DNA during replication in the early embryo. Impaired DNA replication during development can therefore globally derepress chromatin, creating new intergenerationally inherited epigenetic expression states. Overall design: 3 replicates of div-1 mutant worms and N2 wild type worms
Impaired DNA replication derepresses chromatin and generates a transgenerationally inherited epigenetic memory.
Specimen part, Subject
View SamplesThe statins are a family of inhibitors of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase enzyme, which converts acetyl-CoA into mevalonic acid. Since HMG-CoA reductase catalyzes the rate-limiting step in the mevalonate pathway of cholesterol biosynthesis, it was thought that the major clinical benefit of statins was to reduce cholesterol levels in the bloodstream; statins are thus in wide clinical use for the prevention and treatment of cardiovascular disease. Nonetheless, mevalonate is also the precursor of isoprenoid compounds, which are substrates for the post-translational modification of many proteins involved in cell signaling. The blockade of isoprenoid synthesis might explain the pleiotropic effects described for statins in extrahepatic tissues, including inhibition of pathogen infection and anti-inflammatory and immunomodulatory activities.
A lovastatin-elicited genetic program inhibits M2 macrophage polarization and enhances T cell infiltration into spontaneous mouse mammary tumors.
Sex, Specimen part, Treatment
View SamplesProteome and transcriptome often show poor correlation, hindering the system-wide analysis of post-transcriptional regulation. Here, the authors study proteome and transcriptome dynamics during Drosophila embryogenesis and present basic mathematical models describing the temporal regulation of most protein-RNA pairs. Overall design: Whole embryos of Drosophila melanogaster measured at 14 time points during the first 20h of development (0h, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 10h, 12h, 14h, 16h, 18h, 20h). Each sample was measured in biological quadruplicates. RNAseq samples correspond to proteome measurements deposited in ProteomeXchange as PXD005713.
Quantifying post-transcriptional regulation in the development of Drosophila melanogaster.
Specimen part, Cell line, Subject
View Samples