The goal of this experiment is to identify transcripts regulated by Cbc2, the small subunit of nuclear cap binding complex (CBC) in Saccharomyces cerevisiae.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
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View SamplesTo screen for specific circadian outputs that may distinguish the pacemaker in the mammalian suprachiasmatic nucleus (SCN) from peripheral-type oscillators in which the canonical clockworks are similarly regulated in a circadian manner, the rhythmic behavior of the transcriptome in forskolin-stimulated NIH/3T3 fibroblasts was analyzed and compared to that found in the rat SCN in vivo and SCN2.2 cells in vitro. Similar to the scope of circadian gene expression in SCN2.2 cells and the rat SCN, NIH/3T3 fibroblasts exhibited circadian fluctuations in the expression of the core clock genes, Per2, Bmal1 (Mop3), and Cry1 and 323 functionally diverse transcripts (2.6%), many of which were involved in cell communication. Overlap in rhythmically-expressed transcripts among NIH/3T3 fibroblasts, SCN2.2 cells and the rat SCN was limited to these clock genes and four other genes that mediate fatty acid and lipid metabolism or function as nuclear factors. Compared to NIH/3T3 cells, circadian gene expression in SCN oscillators was more prevalent among cellular pathways mediating glucose metabolism and neurotransmission. Coupled with evidence for the rhythmic regulation of the inducible isoform of nitric oxide synthase, the enzyme responsible for the production of nitric oxide, in SCN2.2 cells and the rat SCN but not in fibroblasts, studies examining the effects of a NOS inhibitor on metabolic rhythms in co-cultures containing SCN2.2 cells and untreated NIH/3T3 cells suggest that this gaseous neurotransmitter may play a key role in SCN pacemaker function. Thus, this comparative analysis of circadian gene expression in SCN and non-SCN cells may have important implications in the selective identification of circadian signals involved in the coupling of SCN oscillators and the regulation of rhythmicity in downstream cells or tissues.
Circadian profiling of the transcriptome in NIH/3T3 fibroblasts: comparison with rhythmic gene expression in SCN2.2 cells and the rat SCN.
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View SamplesTo determine whether immortalized cells derived from the rat SCN (SCN 2.2) retain intrinsic rhythm-generating properties characteristic of the SCN, oscillatory properties of the SCN2.2 transcriptome were analyzed and compared to those found in the rat SCN in vivo using rat U34A Affymetrix GeneChips. SCN2.2 cells were expanded in 6-well plates. At 6-hour interval across 2 circadian cycles, cells from single 6-well plates were harvested and pooled for total RNA extraction.
Circadian profiling of the transcriptome in immortalized rat SCN cells.
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View SamplesThe highly aggressive muscle cancer alveolar rhabdomyosarcoma (ARMS) is one of the most common soft tissue sarcoma of childhood, yet the outcome for unresectable and metastatic disease is dismal and unchanged for nearly 3 decades. To better understand the pathogenesis of this disease and to facilitate novel preclinical approaches, we previously developed a conditional mouse model of ARMS by faithfully recapitulating the genetic mutations observed in the human disease, i.e. activation of Pax3:Fkhr fusion gene with either p53 or Cdkn2a inactivation. In this report we show that this model recapitulates the immunohistochemical profile and the rapid progression of the human disease. We demonstrate that Pax3:Fkhr expression increases during late preneoplasia, but that tumor cells undergoing metastasis are under apparent selection for Pax3:Fkhr expression. At a whole genome level, a cross-species gene set enrichment analysis and metagene projection study showed that our mouse model is most similar to human ARMS when compared to other pediatric cancers. We have defined an expression profile conserved between mouse and human ARMS as well as a Pax3:Fkhr signature, including the target gene, SKP2. We further identified 7 druggable kinases over-expressed across species. The data affirms the accuracy of this genetically engineered mouse model.
Credentialing a preclinical mouse model of alveolar rhabdomyosarcoma.
Disease, Disease stage
View SamplesTranscriptomic analysis was performed on the main inflorescence stems of wild-type and lignin-modified lines growing under the same conditions. Study transcriptomic changes in arabidopsis stem manipulated in F5H. Loss of function fah-1 mutant and F5H overexpression (F5H-OE)
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Age, Specimen part
View SamplesGene expression along the crypt-villus (C-V) axis was analyzed using cryostat sectioning to isolate fractions representing the crypts (bottom) and villus tops (top). These fractions were used for analyzing gene expression in iron replete Wistar rats (++), iron deficient Wistar rats (low iron), and in iron deficient Wistar rats fed iron for 3 and 6 days (iron-fed). Differences were observed between the crypts and villus tops in the expression of genes associated with Wnt and BNP signaling, cell proliferation and apoptosis, lipid and iron transport and metabolism. Gene expression in villus crypts and tops was also compared between Wistar and Belgrade rats (bb) and Belgrade rats fed iron (iron-fed) particularly as related to iron absorption and metabolism to define the affects of the mutation in DMT1 in the Belgrade rat on the expression of genes related to iron absorption and metabolism and the response to iron feeding.
Hypoxia-inducible factor-2α and iron absorptive gene expression in Belgrade rat intestine.
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View SamplesStrain differences in gene expression in the hypothalamus of BXD recombinant inbred mice
Sex-specific modulation of gene expression networks in murine hypothalamus.
Sex, Age, Specimen part
View SamplesIslet leukocytic infiltration (insulitis) is first obvious at around 4 weeks of age in the NOD mouse a model for human type 1 diabetes (T1DM). The molecular events leading to insulitis are poorly understood. Since TIDM is caused by numerous genes, we hypothesized that multiple molecular pathways are altered and interact to initiate this disease.
Molecular phenotyping of immune cells from young NOD mice reveals abnormal metabolic pathways in the early induction phase of autoimmune diabetes.
Age, Specimen part
View SamplesType 1 diabetes is a multigenic disease caused by T-cell mediated destruction of the insulin producing -cells. Although conventional (targeted) approaches of identifying causative genes have advanced our knowledge of this disease, many questions remain unanswered. Using a whole molecular systems study, we unraveled the genes/molecular pathways that are altered in CD4 T-cells from young NOD mice prior to insulitis (lymphocytic infiltration into the pancreas). Many of the CD4 T-cell altered genes lie within known diabetes susceptibility regions (Idd), including several genes in the diabetes resistance region Idd13 and two genes (Khdrbs1 and Ptp4a2) in the CD4 T-cell diabetogenic activity region Idd9/11. Alterations involved apoptosis/cell proliferation and metabolic pathways (predominant at 2 weeks), inflammation and cell signaling/activation (predominant at 3 weeks), and innate and adaptive immune responses (predominant at 4 weeks). We identified several factors that may regulate these abnormalities: IRF-1, HNF4A, TP53, BCL2L1 (lies within Idd13), IFNG, IL4, IL15, and prostaglandin E2, which were common to all 3 ages; AR and IL6 to 2 and 4 weeks; and Interferon (IFN-I) and IRF-7 to 3 and 4 weeks. Others were unique to the various ages (e. g. MYC, JUN, and APP to 2 weeks; TNF, TGFB1, NFKB, ERK, and p38MAPK to 3 weeks; and IL12 and STAT4 to 4 weeks). Our data suggest that diabetes resistance genes in Idd13 and Idd9/11, and BCL2L1, IL6-AR and IFNG-IRF-1-IFN-I/IRF-7-IL12 pathways play an important role in CD4 T-cells in the early pathogenesis of autoimmune diabetes. Thus, the alternative approach of investigation at the molecular systems level has captured new information, which combined with validation studies, offers the opportunity to test hypotheses on the role played by the genes/molecular pathways identified in this study, to understand better the mechanisms of autoimmune diabetes in CD4 T-cells, and to develop new therapeutic strategies for the disease.
Molecular pathway alterations in CD4 T-cells of nonobese diabetic (NOD) mice in the preinsulitis phase of autoimmune diabetes.
Age, Specimen part
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