Cockayne syndrome (CS) is an inherited neurodevelopmental disorder with progeroid features. Although the genes responsible for CS have been implicated in a variety of DNA repair- and transcription-related pathways, the nature of the molecular defect in CS remains mysterious. We sought to define this defect by expression analysis of cells lacking functional CSB, a SWI/SNF-like ATPase that is responsible for most CS cases.
Cockayne syndrome group B protein (CSB) plays a general role in chromatin maintenance and remodeling.
Subject
View SamplesPlac1 is an X-linked (Xq26) trophoblast gene expressed at high levels in the placenta, at low levels in the testis, but not in other normal somatic tissues. However, it is re-expressed in several malignancies, including breast, colon, lung, gastric, liver and endometrial cancers as well as in most human cancer cell lines. Plac1 contains HLA-A2-restricted epitopes capable of eliciting a cytotoxic T lymphocyte (CTL) response against human breast cancer cells, and colorectal cancer patients with a Plac1-specific CTL response demonstrate long-term survival. To explore the role of Plac1 in cancer, mouse mammary tumor E0771 cells expressing high levels of Plac1 were transduced with a lentivirus expressing a Plac1 shRNA (E0771/shPlac1).
Plac1 Is a Key Regulator of the Inflammatory Response and Immune Tolerance In Mammary Tumorigenesis.
Cell line
View SamplesDistinct processes govern the transition from myometrial quiescence to activation during both term and preterm labor. We sought the specific gene sets responsible for initiating term and preterm labor, along with a core set of effector genes necessary for labor independent of gestational age and the underlying trigger. The Effector Gene Set consisted of 49 genes present in both preterm and term labor but absent from non-labor samples. 122 genes were specific to preterm labor (Preterm Initiator Set) and 229 to term labor (Term Initiator Set). The Term Initiator and the Effector Sets reflected predominantly inflammatory processes. Surprisingly, the Preterm Initiator Gene Set reflected molecular and biological events almost exclusive of inflammation. Preterm and term labor differ dramatically in their unique, initiator gene profiles, suggesting alternative pathways underlie these events. Inflammatory processes are ubiquitous to the Term Initiator and the Effector Gene Sets, supporting the idea term parturition is an inflammatory process. The absence of inflammatory processes in the Preterm Initiator Set suggests inflammation is secondary to processes triggering spontaneous preterm birth, and could explain the lack of therapeutic efficacy associated with anti inflammatory/antibiotic regimens.
Human effector/initiator gene sets that regulate myometrial contractility during term and preterm labor.
Specimen part
View SamplesRapid responses to biotic and abiotic insults are crucial for plant survival. We examined the very early (10 min) wound transcriptome in order to increase our understanding regarding this critical intial phase of the plant response to stress. Our analysis revealed a rapid induction of stress-related transcripts that was distinct from the long term events which are dominated by jasmonic pathway responses.
Singlet oxygen signatures are detected independent of light or chloroplasts in response to multiple stresses.
Specimen part
View SamplesMicroglia are resident CNS immune cells that are active sensors in healthy brain and versatile effectors under pathological conditions. Cerebral ischemia induces a robust neuroinflammatory response that includes marked changes in the gene expression and phenotypic profile of a variety of endogenous CNS cell types (astrocytes, neurons, microglia) as well as an influx of leukocytic cells (neutrophils, macrophages, T-cells) from the periphery. Many molecules and conditions can trigger a transformation of resting (or surveying) microglia to an activated (alerted/reactive) state. Here we review recent developments in the literature that relate to microglial activation in the experimental setting of in vitro and in vivo ischemia. We also present new data from our own laboratory demonstrating the direct effects of in vitro ischemic conditions on the microglial phenotype and genomic profile. Emphasis is placed on the role of specific molecular signaling systems such as hypoxia inducible factor-1 (HIF-1) and toll-like receptor-4 (TLR4) in regulating the microglial response in this setting. We then review histological and recent novel radiological data that confirms a key role for microglial activation in the setting of ischemic stroke in humans. We discuss recent progress in the pharmacological and molecular targeting of microglia in acute ischemic stroke. Finally, we explore how recent studies on ischemic preconditioning have increased interest in preemptively targeting microglial activation in order to reduce stroke severity.
Microglia in ischemic brain injury.
Specimen part
View SamplesCockayne syndrome is a segmental progeria most often caused by mutations in the CSB gene encoding a SWI/SNF-like ATPase required for transcription-coupled DNA repair (TCR). Over 43 Mya before marmosets diverged from humans, a piggyBac3 (PGBD3) transposable element integrated into intron 5 of the CSB gene. As a result, primate CSB genes now generate both CSB protein and a conserved CSB-PGBD3 fusion protein in which the first 5 exons of CSB are alternatively spliced to the PGBD3 transposase. We show by microarray analysis that expression of the fusion protein alone in CSB-null UV-sensitive syndrome cells (UVSS1KO) cells induces an interferon-like response that resembles both the innate antiviral response and the prolonged interferon response normally maintained by unphosphorylated STAT1 (U-STAT1); moreover, as might be expected based on conservation of the fusion protein, this potentially cytotoxic interferon-like response is largely reversed by coexpression of functional CSB protein. Interestingly, expression of CSB and the CSB-PGBD3 fusion protein together, but neither alone, upregulates the insulin growth factor binding protein IGFBP5 and downregulates IGFBP7, suggesting that the fusion protein may also confer a metabolic advantage, perhaps in the presence of DNA damage. Finally, we show that the fusion protein binds in vitro to members of a dispersed family of 900 internally deleted piggyBac elements known as MER85s, providing a potential mechanism by which the fusion protein could exert widespread effects on gene expression. Our data suggest that the CSB-PGBD3 fusion protein is important in both health and disease, and could play a role in Cockayne syndrome.
The conserved Cockayne syndrome B-piggyBac fusion protein (CSB-PGBD3) affects DNA repair and induces both interferon-like and innate antiviral responses in CSB-null cells.
Specimen part, Cell line
View SamplesThe murine model of Lyme disease provides a unique opportunity to study the localized host response to similar stimulus, B. burgdorferi, in the joints of mice destined to develop severe arthritis (C3H) or mild disease (C57BL/6). Pathways associated with the response to infection and the development of Lyme arthritis were identified by global gene expression patterns using oligonucleotide microarrays. A robust induction of IFN responsive genes was observed in severely arthritic C3H mice at one week of infection, which was absent from mildly arthritic C57BL/6 mice. In contrast, infected C57BL/6 mice displayed a novel expression profile characterized by genes involved in epidermal differentiation and wound repair, which were decreased in the joints of C3H mice. These expression patterns were associated with disease state rather than inherent differences between C3H and C57BL/6 mice, as C57BL/6-IL10-/- mice infected with B. burgdorferi develop more severe arthritis that C57BL/6 mice and displayed an early gene expression profile similar to C3H mice. Gene expression profiles at two and four weeks post infection revealed a common response of all strains that was likely to be important for the host defense to B. burgdorferi and mediated by NF-kB-dependent signaling. The gene expression profiles identified in this study add to the current understanding of the host response to B. burgdorferi and identify two novel pathways that may be involved in regulating the severity of Lyme arthritis.
Gene expression profiling reveals unique pathways associated with differential severity of lyme arthritis.
No sample metadata fields
View SamplesWe assessed the usability of microarrays, which base on formalin-fixed paraffin-embedded (FFPE) tissue.
Systematic evaluation of RNA quality, microarray data reliability and pathway analysis in fresh, fresh frozen and formalin-fixed paraffin-embedded tissue samples.
Specimen part, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Systematic evaluation of RNA quality, microarray data reliability and pathway analysis in fresh, fresh frozen and formalin-fixed paraffin-embedded tissue samples.
Specimen part, Disease
View SamplesWe assessed the feasibility and reliability of microarray studies using formalin-fixed paraffin-embedded (FFPE) tissue-derived RNA compared with transcriptome data from paired fresh-frozen (FF) material. We established a robust workflow to generate highly reproducible microarray datasets from only 2 ng RNA input. For prior quality assessment, inspection of Agilent Bioanalyzer electropherograms, calculation of RNA fragment size distribution (DV200) and routine qPCR for selected references genes were done.
Systematic evaluation of RNA quality, microarray data reliability and pathway analysis in fresh, fresh frozen and formalin-fixed paraffin-embedded tissue samples.
Specimen part
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