The function of Structural maintenance of chromosome flexible domain containing 1 (Smchd1) was examined during mouse preimplantation development using an siRNA knockdown approach. Transient SMCHD1 deficiency during the period between fertilization and morula/early blastocyst stage compromised embryo viability and resulted in reduced cell number, reduced embryo diameter, and reduced nuclear volumes at the morula stage. RNAseq analysis of Smchd1 knockdown morulae revealed aberrant increases in expression of mRNAs related to the trophoblast lineage, indicating SMCHD1 inhibits trophoblast lineage gene expression and promotes inner cell mass formation. siRNA knockdown also reduced expression of cell proliferation genes, including S-phase kinase-associated protein 2 (Skp2). Smchd1 expression was elevated in Caudal type homeobox transcription factor 2 (Cdx2)-/- blastocysts, indicating enriched expression, and further indicating a role in inner cell mass development. These results indicate that Smchd1 plays dual roles in the preimplantation embryo, promoting a lineage-appropriate pattern of gene expression supporting inner cell mass formation, whilst controlling lineage formation and gene expression in the trophectoderm. Overall design: Effects of SMCHD1 siRNA knockdown were tested in mouse embryos
Novel key roles for structural maintenance of chromosome flexible domain containing 1 (Smchd1) during preimplantation mouse development.
Treatment, Subject
View SamplesThe aim of this study was to determine how gene expression is changed after arsenite-induced malignant transformation of prostate epithelial cells.
Coordinate H3K9 and DNA methylation silencing of ZNFs in toxicant-induced malignant transformation.
Specimen part, Cell line, Treatment
View SamplesComparing WT mice to a mouse model of mental retardation, this work identifies genes which display differences in ribosome-bound mRNAs, in hippocampus CA1 pyramidal cells. These genes products are potent functional components of neuronal plasticity and hippocampus-dependent memory. Overall design: Using a triple transgenic mouse line, we immunoprecipitated the HA-Rpl22 protein to isolate and sequence ribosome-associated mRNA in CA1 pyramidal cells. Pairwise comparison of wild type and Fmr1 KO mice defined a specific gene expression profile.
Cell Type-Specific mRNA Dysregulation in Hippocampal CA1 Pyramidal Neurons of the Fragile X Syndrome Mouse Model.
Specimen part, Subject
View SamplesIn order to analyze the global changes in gene expression resulting from loss of Fra signaling, we performed a microarray experiment comparing Drosophila embryos containing a loss of function fra[3] mutation to age matched wildtype
Requirement for commissureless2 function during dipteran insect nerve cord development.
Specimen part
View SamplesIn order to analyze the global changes in gene expression resulting from induction of NetA-Fra signaling, we carried out a microarray experiment comparing Drosophila third instar wing imaginal discs in which Net+Fra had been overexpressed to age matched wild type wing imaginal discs.
Requirement for commissureless2 function during dipteran insect nerve cord development.
Specimen part
View SamplesMania is a serious neuropsychiatric condition associated with significant morbidity and mortality. Previous studies have suggested that environmental exposures can contribute to mania pathogenesis. We measured dietary exposures in a cohort of individuals with mania and other psychiatric disorders as well as in control individual without a psychiatric disorder. We found that a history of eating nitrated dry cured meat, but not other meat or fish products, was strongly and independently associated with current mania (adjusted odds ratio 3.49, 95% confidence interval (CI) 2.24-5.45, p<8.97x 10-8). Lower odds of association were found between eating nitrated dry cured meat and other psychiatric disorders. We further found that the feeding of meat preparations with added nitrate to rats resulted in alterations in behavior and changes in intestinal microbiota. Rats fed diets with added nitrate also showed alterations of brain pathways dysregulated in mania. These findings may lead to new methods for preventing mania and for developing novel therapeutic interventions
Nitrated meat products are associated with mania in humans and altered behavior and brain gene expression in rats.
Sex, Specimen part
View SamplesThe mammalian gastrointestinal tract harbors thousands of bacterial species that include symbionts as well as potential pathogens. The immune responses that limit access of these bacteria to underlying tissue remain poorly defined.
Gammadelta intraepithelial lymphocytes are essential mediators of host-microbial homeostasis at the intestinal mucosal surface.
Specimen part
View SamplesPurpose:Next-generation sequencing has revolutionized sytems-level celluar pathway analysis. The goals of this study are to compare the U87 cell xenograft GBM mice (U87 cell line) to TWIST1 knock out U87 cell xenograft GBM mice (TWIST1 knock out U87 cell line) using their transcriptomes Overall design: Methods: Investigation of TWIST1 expression on glioblastoma malignancy in vitro and in vivo.
Targeting TWIST1 through loss of function inhibits tumorigenicity of human glioblastoma.
Specimen part, Subject
View SamplesIn order to determine the imprinted transcription factor Zac1 targets, we overexpressed Zac1 in a mouse insulinoma cell line and measured the regulated expressed genes by RNA-seq. We have shown that Zac1 regulates many genes belonging to the Imprinted Gene Network, including genes coding for the extra-cellular matrix. Overall design: Determination of Zac1 target genes in transfected Min6 cells (4 biological replicates) using RNA-seq, .
Identification of Plagl1/Zac1 binding sites and target genes establishes its role in the regulation of extracellular matrix genes and the imprinted gene network.
Specimen part, Subject
View SamplesHuman mucosal surfaces contain a wide range of microorganisms. The biological effects of these organisms are largely unknown. Large-scale metagenomic sequencing is emerging as a method to identify novel microbes. Unexpectedly, we identified DNA sequences homologous to virus ATCV-1, an algal virus not previously known to infect humans, in oropharyngeal samples obtained from healthy adults. The presence of ATCV-1 was associated with a modest but measurable decrease in cognitive functioning. A relationship between ATCV-1 and cognitive functioning was confirmed in a mouse model, which also indicated that exposure to ATCV-1 resulted in changes in gene expression within the brain. Our study indicates that viruses in the environment not thought to infect humans can have biological effects.
Chlorovirus ATCV-1 is part of the human oropharyngeal virome and is associated with changes in cognitive functions in humans and mice.
Treatment
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