Our study looks at the dirsruption of lung circadian transcriptome that occurs when neutrophils are depleted (by application of antibodies (anti-Ly6G-1A8) to wildtype C57BL/6 mice, or Diphtheria toxin (DT) to neutrophil-specific DT-susceptible mice (MRP8-Cre;iDTR-flox)). Overall design: Lungs were harvested from neutrophil-depleted (antibody or DT) or non-depleted mice, in normal light-controlled mouse facility (ZT4) or 12h inverted light cabinets (ZT16). Experiments were carried out over 3 batches (July 2017, September 2017, and April 2018), with 3 or 4 mice per group. Antibody-depleted and non-depleted mice were tested for the July 2017 and September 2017 batches, whereas DT-depleted mice were tested only in April 2018.
Neutrophils instruct homeostatic and pathological states in naive tissues.
Specimen part, Treatment, Subject
View SamplesThe SnRK1 protein kinase, the plant ortholog of mammalian AMPK and yeast Snf1, is activated by the energy depletion caused by adverse environmental conditions. Upon activation, SnRK1 triggers extensive transcriptional changes to restore homeostasis and promote stress tolerance and survival partly through the inhibition of anabolism and the activation of catabolism. Despite the identification of a few bZIP transcription factors as downstream effectors, the mechanisms underlying gene regulation, and in particular gene repression by SnRK1, remain mostly unknown. microRNAs (miRNAs) are 20-24nt RNAs that regulate gene expression post-transcriptionally by driving the cleavage and/or translation attenuation of complementary mRNA targets. In addition to the well-established role of miRNAs as regulators of plant development, mounting evidence implicates miRNAs in the response to environmental stress. Given the involvement of miRNAs in stress responses and the fact that some of the SnRK1-regulated genes are miRNA targets, we postulated that miRNAs drive part of the transcriptional reprogramming triggered by SnRK1 activation. To test this we have performed comparative analyses of the transcriptional response to energy deprivation between WT and dcl1-9, a mutant deficient in miRNA biogenesis.
miRNAs mediate SnRK1-dependent energy signaling in Arabidopsis.
Specimen part, Treatment
View SamplesAnalysis to identify genome-wide differential alternative splicing events in A549 cells in which the levels of the gene SRSF1 were down-regulated with a specific siRNA
Identification of alternative splicing events regulated by the oncogenic factor SRSF1 in lung cancer.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Prenatal arsenic exposure and the epigenome: altered microRNAs associated with innate and adaptive immune signaling in newborn cord blood.
Specimen part
View SamplesThe Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gmez Palacio, Mexico was recently established to better understand the impacts of prenatal exposure to inorganic arsenic (iAs). In this study, we examined a subset (n=40) of newborn cord blood samples for microRNA (miRNA) expression changes associated with in utero arsenic exposure. Levels of iAs in maternal drinking water (DW-iAs) and maternal urine were assessed. Levels of DW-iAs ranged from below detectable values to 236 g/L (mean=51.7 g/L). Total arsenic in maternal urine (U-tAs) was defined as the sum of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) and ranged from 6.2 to 319.7 g/L (mean=64.5 g/L). Genome-wide miRNA expression analysis of cord blood revealed 12 miRNAs with increasing expression associated with U-tAs. Transcriptional targets of the miRNAs were computationally predicted and subsequently assessed using transcriptional profiling. Pathway analysis demonstrated that the U-tAs-associated miRNAs are involved in signaling pathways related to known health outcomes of iAs exposure including cancer and diabetes mellitus. Immune response-related mRNAs were also identified with decreased expression levels associated with U-tAs, and predicted to be mediated in part by the arsenic-responsive miRNAs. Results of this study highlight miRNAs as novel responders to prenatal arsenic exposure that may contribute to associated immune response perturbations.
Prenatal arsenic exposure and the epigenome: altered microRNAs associated with innate and adaptive immune signaling in newborn cord blood.
Specimen part
View SamplesThere is an increasing interest on the role of Alternative splicing (AS) in different pathologies. The Affymetrix Human Transcriptome Array (HTA 2.0) can be used to explore AS very efficiently. However, the interpretation software provided by its vendor (TAC 3.0) does not fully exploit its potential and can only be applied to case-control studies. EventPointer is an R package to identify Alternative Splicing events using HTA 2.0 arrays. It can be applied to complex experimental designs. The software provides a list of the detected events indicating the type of event (cassette, alternative 3, etc.), their statistical significance, and affected protein domains affected. The false positive rate is very low (the first detected false positive was ranked in the 149th position). EventPointer is publicly available at GitHub.
EventPointer: an effective identification of alternative splicing events using junction arrays.
Cell line
View SamplesRibosome profiling of MDA-MB-231 cells treated with Silvestrol to monitor transcriptome wide, eIF4A-dependent changes in translation efficiency Overall design: Translation efficiency (TE) of mRNAs dervied from ribosome footprints was monitored in the presence or absence of 25 nM Silvestrol, an inhibitor of eukaryotic translation initiation factor 4A (eIF4A). Transcripts with reduced TE in the presence of Silvestrol were compare to transcripts with reduced TE in the presence of INK128, a catalytic mTOR inhbitor.
Transcriptome-wide characterization of the eIF4A signature highlights plasticity in translation regulation.
No sample metadata fields
View SamplesTumors from pancreatic cancer specimens obtained at surgery were used for efficacy testing and biologic analysis
Coordinated epidermal growth factor receptor pathway gene overexpression predicts epidermal growth factor receptor inhibitor sensitivity in pancreatic cancer.
No sample metadata fields
View SamplesStudy the role of klotho as a tumor suppressor in colorectal cancer.
Klotho suppresses colorectal cancer through modulation of the unfolded protein response.
Cell line
View SamplesWhile pathogen-induced immunity is comparatively well characterized, far less is known about plant defense responses to arthropod herbivores. To date, most molecular-genetic studies of plant-arthropod interactions have focused on insects. However, plant-feeding (phytophagous) mites are also pests of diverse plants, and mites induce different patterns of damage to plant tissues than do well-studied insects (e.g., Lepidopteran larvae or aphids). The two-spotted spider mite, Tetranychus urticae, is among the most significant mite pests in agriculture. T. urticae is an extreme generalist that has been documented on a staggering number of plant hosts (more than 1,100), and is renowned for the rapid evolution of pesticide resistance. To understand reciprocal interactions between T. urticae and a plant host at the molecular level, we examined mite herbivory using Arabidopsis thaliana. Despite differences in feeding guilds, we found that transcriptional responses of A. thaliana to mite herbivory generally resembled those observed for insect herbivores. In particular, defense to mites was mediated by jasmonic acid (JA) biosynthesis and signaling. Further, indole glucosinolates dramatically increased mite mortality and development times. Variation in both basal and activated levels of these defense pathways might also explain differences in mite damage and feeding success between A. thaliana accessions. On the herbivore side, a diverse set of genes associated with detoxification of xenobiotics was induced upon exposure to increasing levels of in planta indole glucosinolates. Our findings provide molecular insights into the nature of, and response to, herbivory for a representative of a major class of arthropod herbivores.
Reciprocal responses in the interaction between Arabidopsis and the cell-content-feeding chelicerate herbivore spider mite.
Age, Specimen part, Treatment
View Samples