Sleep deprivation (SD) in young adults is associated with metabolic, stress and cognitive responses that are also characteristic of brain aging. Given that sleep architecture changes with age, including increased fragmentation and decreased slow wave activity, it seems reasonable to investigate potential molecular relationships between SD and aging in brain tissue. Here, we tested the hypothesis that young rats exposed to 24 or 72 hour SD would respond with stress and aging-like shifts in brain hippocampal CA1 gene expression. SD animals showed blood corticosterone and weight changes consistent with a stress response. Microarray results, validated by Western blot and comparison to prior SD studies, pointed to disruptions in neurotransmission, sleep pressure signaling, and macromolecular synthesis. In a separate experiment, animals exposed to 24 or 72 hour novel environment stress recapitulated nearly one third of the SD transcriptional profile, particularly upregulated apoptotic and immune signaling pathways. Compared to aging (based on three previously published independent hippocampal aging studies), SD transcriptional profiles agreed for neurogenesis and energy pathways. However, immune signaling, glial activity, macromolecular synthesis and neuronal function all showed an SD profile that was, at least in part, opposed by aging. We conclude that while stress and SD have discrete molecular signatures, they do show a subset of highly similar changes. However, the same could not be said of aging and SD, where a similar subset of genes is changed, but in partially divergent directions. Finally, this work identifies presynaptic vesicular release and intercellular adhesion molecular signatures as novel targets for future SD-countering therapeutics.
Hippocampal CA1 transcriptional profile of sleep deprivation: relation to aging and stress.
Sex, Treatment
View SamplesWe found that MPLA reprograms macrophages in a way that supports a persistent monocyte/macrophage chemokine secretion profile reflected in macrophage mRNA. Additionally, this RNA-seq data revealed that certain genes (e.g. phagocytosis-related) persist much longer after MPLA than others (e.g. pro-inflammatory cytokines). Overall design: Bone marrow derived macrophages were harvested for RNA after 4hrs of monophosphoryl lipid A (MPLA) priming, 24hrs of MPLA priming, and 3 days following the end of priming
The TLR4 Agonist Monophosphoryl Lipid A Drives Broad Resistance to Infection via Dynamic Reprogramming of Macrophage Metabolism.
Cell line, Subject
View SamplesSmall non-coding RNAs (sncRNAs) have been proposed as potential vectors of the interface between genes and environment. Here, we report that environmental conditions involving traumatic stress in early life, alter miRNA and piRNA composition in sperm of adult males in mice. Overall design: Examination of small RNA content of sperm from males, that experienced early chronic stress during their first two weeks of life versus small RNA content of sperm from control males.
Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice.
Sex, Disease, Cell line, Subject
View SamplesPlant compensatory responses depends on transcriptional reprogramming. We used microarray analysis to understand the differential gene expression pattern between clipped (herbivore browsed)
Overcompensation in response to herbivory in Arabidopsis thaliana: the role of glucose-6-phosphate dehydrogenase and the oxidative pentose-phosphate pathway.
Specimen part
View SamplesHigh MC-SFA intake resulted in a downregulation of gene expression of pathways related to complement system and inflammation, and an upregulation of gene expression of pathways related to citric acid cycle, electron transport chain and lipid metabolism in adipose tissue. Based on our results, we hypothesize that the beneficial effects of MC-SFAs on prevention of fat accumulation may be mediated by increases in gene expression related to energy metabolism in the adipose tissue. Additionally, decreases in inflammation-related gene expression in the adipose may potentially have beneficial effects in relation to cardiometabolic diseases.
Dietary medium-chain saturated fatty acids induce gene expression of energy metabolism-related pathways in adipose tissue of abdominally obese subjects.
Sex, Age, Specimen part, Subject
View SamplesParadoxical cryptococcosis-associated immune reconstitution inflammatory syndrome
Transcriptomic Predictors of Paradoxical Cryptococcosis-Associated Immune Reconstitution Inflammatory Syndrome.
Specimen part
View SamplesPre-leukemic mutations are thought to promote clonal expansion of hematopoietic stem cells (HSCs) by increasing self-renewal and competitiveness. However, mutations that increase HSC proliferation tend to reduce competitiveness and self-renewal potential, raising the question of how a mutant HSC can sustainably outcompete wild-type HSCs. Activating mutations in NRAS are prevalent in human myeloproliferative disease and leukemia. Here we show that a single allele of oncogenic NrasG12D increases HSC proliferation but also increases reconstituting and self-renewal potential upon serial transplantation in irradiated mice, all without immortalizing HSCs or causing leukemia in our experiments. NrasG12D also confers long-term self-renewal potential upon multipotent progenitors. To explore the mechanism by which NrasG12D promotes HSC proliferation and self-renewal we assessed HSC cell cycle kinetics using H2B-GFP label retention. We found that NrasG12D had a bimodal effect on HSCs, increasing the proliferation of some HSCs while increasing the quiescence and competitiveness of other HSCs. One signal can therefore increase HSC proliferation, competitiveness, and self-renewal through a bimodal effect that promotes proliferation in some HSCs and quiescence in others.
Oncogenic Nras has bimodal effects on stem cells that sustainably increase competitiveness.
Specimen part
View SamplesWe utilized oligonucleotide microarrays to measure cellular mRNA decay rates in mock- or reovirus-infected murine L929 cells to determine if changes in host mRNA expression are a consequence of reovirus-induced alterations in cellular mRNA stability.
Reovirus infection induces stabilization and up-regulation of cellular transcripts that encode regulators of TGF-β signaling.
Cell line, Time
View SamplesDifferentiation of naive CD8 T cells into cytotoxic effector cells requires three distinct signals- antigen (signal 1), costimulation -B7-1 (signal 2) and cytokine, either interleukin-12 or interferon-a/b (signal 3). Interaction of naive CD8 T cells with antigen and B7-1 programs cell division and proliferation whereas the presence of cytokines- IL-12 or IFNa/b promote survival, differentiation and memory establishment. In the absence of signal 3, the cells interacting with antigen/B7-1 undergo tolerance induction. The objective of this study was to elucidate the mechanisms how the provision of signal 3 promotes differentiation and averts tolerance induction in CD8 T cells. Trichostatin A is a pharmacological agent that inhibits histone deacetylase activity, hence regulating chromatin structure and gene expression and differentiation in many cell types. Gene signature profiles of IL-12, IFNa/b and trichostatin A stimulated cells were compared to elucidate the molecular mechanisms of gene regulation.
Gene regulation and chromatin remodeling by IL-12 and type I IFN in programming for CD8 T cell effector function and memory.
Age, Specimen part, Time
View SamplesExternal stimulations of cells by hormones, growth factors or cytokines activate signal transduction pathways that subsequently induce a rearrangement of cellular gene expression. The representation and analysis of changes in the gene response is complicated, and essentially consists of multiple layered temporal responses. In such situations, matrix factorization techniques may provide efficient tools for the detailed temporal analysis. Related methods applied in bioinformatics intentionally do not take prior knowledge into account. In signal processing, factorization techniques incorporating data properties like second-order spatial and temporal structures have shown a robust performance. However, large-scale biological data rarely imply a natural order that allows the definition of an autocorrelation function. We therefore develop the concept of graph-autocorrelation. We encode prior knowledge like transcriptional regulation, protein interactions or metabolic pathways as a weighted directed graph. By linking features along this underlying graph, we introduce a partial ordering of the samples to define an autocorrelation function. Using this framework as constraint to the matrix factorization task allows us to set up the fast and robust graph decorrelation (GraDe) algorithm. To analyze the alterations in the gene response in IL-6 stimulated primary mouse hepatocytes by GraDe, a time-course microarray experiment was performed. Extracted gene expression profiles show that IL-6 activates genes involved in cell cycle progression and cell division in a time-resolved manner. On the contrary, genes linked to metabolic and apoptotic processes are down-regulated indicating that IL-6 mediated priming rendered hepatocytes more responsive towards cell proliferation and reduces expenses for the energy household.
Knowledge-based matrix factorization temporally resolves the cellular responses to IL-6 stimulation.
Specimen part, Treatment, Time
View Samples