PRMT5 is a type II protein arginine methyltransferase (PRMT) with roles in cancer, reprogramming and neurogenesis. In pluripotent stem cells PRMT5 prevents naïve stem cell differentiation however its role in ground state pluripotency is unknown. Our goal of this study is to demonstrate the essential role of PRMT5 in ground state pluripotency and PGC development.
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View SamplesGene expression profiles of malignant carcinomas surgically removed from ovarian cancer patients pre-treated with chemotherapy (neo-adjuvant) prior to surgery group into two distinct clusters. One group clusters with carcinomas from patients not pre-treated with chemotherapy prior to surgery (C-L) while the other clusters with non-malignant adenomas (A-L).
Evidence that p53-mediated cell-cycle-arrest inhibits chemotherapeutic treatment of ovarian carcinomas.
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View SamplesIn contrast to epithelial derived carcinomas that arise in most human organs, ovarian surface epithelial cells become more rather than less differentiated as the malignancy progresses. To test the hypothesis that ovarian surface epithelial cells retain properties of relatively uncommitted pluripotent cells until undergoing neoplastic transformation, we conducted gene expression profiling analysis (Affymetrix, U133 Plus 2.0) of 12 ovarian surface epithelial cells and 12 laser capture microdissected serous papillary ovarian cances. We find that over 2000 genes are significantly differentially expressed between the surface epithelial and cancer samples. Network analysis implicates key signaling pathways and pathway interactions in ovarian cancer development. Genes previously associated with adult stem cell maintenance are expressed in ovarian surface epithelial cells and significantly down-regulated in ovarian cancer cells. Our results indicate that the surface of the ovary is an adult stem cell niche and that deregulation of genes involved in maintaining the quiescence of ovarian surface epithelial cells is instrumental in the initiation and development of ovarian cancer.
Gene expression profiling supports the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as ovarian cancer initiating cells.
Disease, Disease stage
View SamplesGene expression analyses of pancreatic adenocarcinoma and adjacent ductal epithelia from the same patient using bulk vs LCM dissected samples.
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Specimen part, Disease, Disease stage
View SamplesDuring embryogenesis, cell specification and tissue formation is directed by the concentration and temporal presentation of morphogens, and similarly, pluripotent embryonic stem cells differentiate in vitro into various phenotypes in response to morphogen treatment. Embryonic stem cells are commonly differentiated as three dimensional spheroids called embryoid bodies (EBs); however, differentiation within EBs is typically heterogeneous and disordered. Here we show that spatiotemporal control of microenvironmental cues embedded directly within EBs enhances the homogeneity, synchrony and organization of differentiation. Degradable polymer microspheres releasing retinoic acid within EBs induce the formation of cystic spheroids closely resembling the early streak mouse embryo, with an exterior of visceral endoderm enveloping an epiblast layer. These results demonstrate that controlled morphogen presentation to stem cells more efficiently directs cell differentiation and tissue formation, thereby improving developmental biology models and enabling the development of regenerative medicine therapies and cell diagnostics.
Homogeneous and organized differentiation within embryoid bodies induced by microsphere-mediated delivery of small molecules.
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View SamplesCoMet, a fully automated Computational Metabolomics method to predict changes in metabolite levels in cancer cells compared to normal references has been developed and applied to Jurkat T leukemia cells with the goal of testing the following hypothesis: up or down regulation in cancer cells of the expression of genes encoding for metabolic enzymes leads to changes in intracellular metabolite concentrations that contribute to disease progression. Nine metabolites predicted to be lowered in Jurkat cells with respect to normal lymphoblasts were examined: riboflavin, tryptamine, 3-sulfino-L-alanine, menaquinone, dehydroepiandrosterone, -hydroxystearic acid, hydroxyacetone, seleno-L-methionine and 5,6-dimethylbenzimidazole. All, alone or in combination, exhibited antiproliferative activity. Of eleven metabolites predicted to be increased or unchanged in Jurkat cells, only two (bilirubin and androsterone) exhibited significant antiproliferative activity. These results suggest that cancer cell metabolism may be regulated to reduce the intracellular concentration of certain antiproliferative metabolites, resulting in uninhibited cellular growth and have the implication that many other endogenous metabolites with important roles in carcinogenesis are awaiting discovery.
Identification of metabolites with anticancer properties by computational metabolomics.
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View SamplesMaize exhibits levels of structural variation (SV) of non-repeat sequences that are unprecedented among higher eukaryotes. This SV includes hundreds of copy number variants (CNVs) and thousands of presence/absence variants (PAVs). Many of the PAVs contain intact, expressed, single-copy genes that are present in one haplotype but absent from another. The goal of this project is to test the hypothesis that differences in gene copy number (both gains and losses) contribute to the extraordinary phenotypic diversity and plasticity of maize. Maize is a good model for these studies because it exhibits a rapid decay of linkage disequilibrium (LD) and because a draft genome sequence of the B73 inbred and mapping populations are available. As a first step, the "Zeanome", a near-complete set of genes present in B73, other maize lines and the wild ancestor of maize (teosinte), is being defined using transcriptomic data.
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View SamplesNo description.
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Cell line
View SamplesRNA-seq transcriptome profiles of genetically fate-mapped serotonin neurons, manually sorted from multiple anatomic domains, at both population and single cell resolution.
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Sex, Specimen part, Cell line
View SamplesHeterosis which is the improved vigor of F1-hybrids compared to their parents is widely exploited in maize (Zea mays L.) breeding to produce elite hybrids of superior yield. The transcriptomes of the maize inbred lines B73 and Mo17 and their reciprocal hybrid offspring were surveyed in the meristematic zone, the elongation zone, cortex and stele tissues of primary roots, prior to the developmental manifestation of heterosis. Single parent expression (SPE) is consistent with the dominance model for heterosis in that it denotes genes that are expressed in only one parent but in both reciprocal hybrids. In primary root tissues, between 1,027 (elongation zone) and 1,206 (stele) SPE patterns were observed. As a consequence, hybrids displayed in each tissue >400 active genes more than either parent. Analysis of tissue-specific SPE dynamics revealed that 1,233 of 2,233 SPE genes displayed SPE in all tissues in which they were expressed while 1,000 SPE genes displayed in at least one tissue a non-SPE pattern. In addition, 64% (17,351/ 27,164) of all expressed genes were assigned to the two subgenomes which are the result of an ancient genome duplication. By contrast, only between 18 and 25% of the SPE genes were assigned to a subgenome suggesting that a disproportionate number of SPE genes are evolutionary young and emerged after genome duplication. We hypothesize that this phenomenon is associated with human selection of favorable maize genotypes which might primarily affect younger genes rather than genes whose functions have been conserved for millions of years.
Nonsyntenic genes drive highly dynamic complementation of gene expression in maize hybrids.
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