Exogenous 17-estradiol (E2) accelerates the progression of ovarian cancer in the transgenic tgCAG-LS-TAg mouse model of the disease. We hypothesized that E2 has direct effects on ovarian cancer cells and this study was designed to determine the molecular mechanisms by which E2 accelerates ovarian tumour progression. Mouse ovarian cancer ascites (MASE2) cell lines were derived from tgCAG-LS-TAg mice. Following intraperitoneal engraftment of MASE2 into SCID mice, exogenous E2 significantly decreased the survival time and increased the tumour burden.
17β-estradiol upregulates GREB1 and accelerates ovarian tumor progression in vivo.
No sample metadata fields
View SamplesWe use single-cell RNA sequencing (scRNA-seq) to explore the transcriptional changes associated with estrogen-induced dysplasia in mouse ovarian surface epithelial cells Overall design: scRNA-seq of control and estrogen-treated (100nM) mOSE cultured for 15 days. scRNA-seq was performed using the Fluidigm HT 3' RNA-seq protocol on the Fluidigm C1
Single-cell RNA-sequencing reveals transcriptional dynamics of estrogen-induced dysplasia in the ovarian surface epithelium.
Specimen part, Treatment, Subject
View SamplesExamined gene expression changes in a histone H2A R78A mutant in Saccharomyces cerevisiae relative to wild-type cells. THe overall goal of this study was to determine the functions of histone 'sprocket' arginine residues, which insert into the DNA minor groove in the nucleosome. We examined the roles of sprocket arginine mutants in gene expression, histone incorporation, and DNA repair.
Histone Sprocket Arginine Residues Are Important for Gene Expression, DNA Repair, and Cell Viability in Saccharomyces cerevisiae.
No sample metadata fields
View SamplesHD R6/1 transgenic mouse line brain hemispheres dissected. RNA targets were created for transgenics and wildtypes at time points 18, 22 and 27 weeks. Profiles and data analysis performed using the Bioconductor software and linear model contrasts using LIMMA on RMA probeset summarys.
Brain gene expression correlates with changes in behavior in the R6/1 mouse model of Huntington's disease.
No sample metadata fields
View SamplesThe purpose of this study was to determine the pathogenic changes that occur in myoepithelial cells (MECs) from lacrimal glands of a mouse model of Sjogren’s syndrome. MECs were cultured from lacrimal glands of C57BL/6J (wild type, WT), and thrombospondin 1 knockout null (TSP1 -/- ) mice.
Lacrimal Gland Myoepithelial Cells Are Altered in a Mouse Model of Dry Eye Disease.
Sex
View SamplesWe performed RNA-seq 72 h after acute deletion of Smarca4 in a line of conditional knockout mouse embryonic stem cells to examine altered gene expression. Overall design: Examination of mRNA in mouse embryonic stem cells expressing conditional knockout of the mSWI/SNF ATPase Smarca4. For these studies, mRNA was harvested from Smarca4-CreER (Smarca4flfl) conditional knockout cells 72 h after treatment with either ethanol (EtOH) or 0.8 uM 4-hydroxytamoxifen (Tam).
Smarca4 ATPase mutations disrupt direct eviction of PRC1 from chromatin.
Specimen part, Subject
View SamplesHistone deacetylase 3 (HDAC3) is the catalytic component of NCoR/SMRT corepressor complexes that mediate the actions of transcription factors implicated in the regulation of B cell development and function. We crossed Hdac3 conditional knockout mice with Mb1-Cre knockin animals to delete Hdac3 in early progenitor B cells. The spleens of Hdac3F/-Mb1-Cre+/- mice were virtually devoid of mature B cells, and B220+CD43+ B cell progenitors accumulated within the bone marrow. Quantitative deep sequencing of the immunoglobulin heavy chain locus from B220+CD43+ populations identified a defect in VHDJH recombination with a severe reduction in productive rearrangements, which directly corresponded to the loss of pre-B cells from Hdac3D/- bone marrow. For Hdac3D/- B cells that did show productive VDJ rearrangement, there was significant skewing toward the incorporation of proximal VH gene segments and a corresponding reduction in distal VH gene segment usage. While transcriptional effects within these loci were modest, Hdac3D/- progenitor cells displayed global changes in chromatin structure that likely hindered effective distal V-DJ recombination. Re-introduction of wild type Hdac3 restored normal B cell development, whereas an Hdac3 point mutant lacking deacetylase activity failed to complement this defect. Thus, the deacetylase activity of Hdac3 is required for the generation of mature B cells. Overall design: Bone marrow was isolated from Hdac3+/+Mb1cre+/- or Hdac3F/-Mb1cre+/- mice at 8 weeks of age. B220+CD43+ B cells were isolated from marrow by FACS and cells from two mice were pooled per sample. Total RNA isolated by Trizol extraction.
Deacetylase activity of histone deacetylase 3 is required for productive <i>VDJ</i> recombination and B-cell development.
Specimen part, Cell line, Subject
View SamplesMethamphetamine (METH) is an illicit drug which is neurotoxic to the mammalian brain. Numerous studies have revealed significant decreases in dopamine and serotonin levels in the brains of animals exposed to moderate-to-large METH doses given within short intervals of time. In contrast, repeated injections of small nontoxic doses of the drug followed by a challenge with toxic METH doses afford significant protection against monoamine depletion. The present study was undertaken to test the possibility that repeated injections of the drug might be accompanied by transcriptional changes involved in rendering the nigrostriatal dopaminergic system refractory to METH toxicity. Our results confirm that METH preconditioning can provide significant protection against METH-induced striatal dopamine depletion. In addition, the presence and absence of METH preconditioning were associated with substantial differences in the identity of the genes whose expression was affected by a toxic METH challenge.
Methamphetamine preconditioning alters midbrain transcriptional responses to methamphetamine-induced injury in the rat striatum.
Sex, Age, Specimen part, Treatment
View SamplesDC-SIGN is a C-type lectin expressed by dendritic cells (DCs) that binds HIV-1, sequestering it within multivesicular bodies to facilitate transmission to CD4+ T cells. Here we characterize the molecular basis of signalling through DC-SIGN by large-scale gene expression profiling and phosphoproteome analysis. Solitary DC-SIGN activation leads to a phenotypically disparate transcriptional program from Toll-like receptor (TLR) triggering with downregulation of MHC II, CD86, and interferon response genes and with induction of the TLR negative regulator ATF3. Phosphoproteome analysis reveals DC-SIGN signals through the leukemia-associated Rho guanine nucleotide exchange factor (LARG) to induce Rho activity. This LARG activation also occurs on DC HIV exposure and is required for effective HIV viral synapse formation. Taken together HIV mediated DC-SIGN signalling provides a mechanism by which HIV evades the immune response yet induces viral spread.
Activation of the lectin DC-SIGN induces an immature dendritic cell phenotype triggering Rho-GTPase activity required for HIV-1 replication.
No sample metadata fields
View Samplespancreas islet single-cell RNA-seq Overall design: isolated from 2 wt
Neurog3-Independent Methylation Is the Earliest Detectable Mark Distinguishing Pancreatic Progenitor Identity.
Specimen part, Subject
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