Identification of genetic/cytogenetic alterations and differentially expressed cellular genes in HPV16 E6, E7 and E6/E7 positive human foreskin keratinocytes
Complementation of non-tumorigenicity of HPV18-positive cervical carcinoma cells involves differential mRNA expression of cellular genes including potential tumor suppressor genes on chromosome 11q13.
No sample metadata fields
View SamplesIdentification of genes differentially expressed in tumorigenic compared to non-tumorigenic, HPV18 positive cells
Complementation of non-tumorigenicity of HPV18-positive cervical carcinoma cells involves differential mRNA expression of cellular genes including potential tumor suppressor genes on chromosome 11q13.
No sample metadata fields
View SamplesThe goal of this study was to examine whether immune responses to Plasmodium chabaudi infection differ between the sexes and are altered by the presence of gonadal steroids. Gonadally-intact males were more likely than intact females to die following P. chabaudi infection, exhibit slower recovery from infection-associated weight loss, hypothermia, and anemia, have reduced IFN-associated gene expression and IFN production during peak parasitemia, and produce less antibody during the recovery phase of infection. Gonadectomy of male and female mice altered these sex-associated differences, suggesting that sex steroid hormone, in particular androgens and estrogens, may modulate immune responses to infection.
Involvement of gonadal steroids and gamma interferon in sex differences in response to blood-stage malaria infection.
No sample metadata fields
View SamplesThe experiment was to compare leukemic T cells from thymic lymphomas from homozygote mice for the IkL/L hypomorphic mutation and non-transformed thymocytes, either of WT or IkL/L genotype. The aim was to identify a gene expression signature specific to the IkL/L tumors.
Notch activation is an early and critical event during T-Cell leukemogenesis in Ikaros-deficient mice.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Large-scale hypomethylated blocks associated with Epstein-Barr virus-induced B-cell immortalization.
Specimen part, Time
View SamplesTo determine what DNA methylation and gene expression changes occur following EBV transformation. B-cells were isolated from 3 donors. Resting, CD40 activated and EBV transfromed cells from each donor was analyzed. Each sample was assayed using Affymetrix expression arrays and whole genome bisulfite sequenicng. Additional time points during transformation and activation were sequenced as well, but not assayed for expression.
Large-scale hypomethylated blocks associated with Epstein-Barr virus-induced B-cell immortalization.
Specimen part
View SamplesOf the members of mitochondrial transcription termination factors (mTERFs) found in metazoans and plants known to regulate organellar gene expression at various levels, plant mTERF6 promotes maturation of a tRNA
Definition of a core module for the nuclear retrograde response to altered organellar gene expression identifies GLK overexpressors as gun mutants.
No sample metadata fields
View SamplesRNA polymerase III (Pol III) is an essential enzyme responsible for the synthesis of several small non-coding RNAs, a number of which are involved in mRNA translation. Recessive mutations in POLR3A, encoding the largest subunit of Pol III, cause POLR3-related hypomyelinating leukodystrophy (POLR3-HLD), characterized by deficient central nervous system myelination. Identification of the downstream effectors of pathogenic POLR3A mutations has been so far elusive. Here, we used CRISPR-Cas9 to introduce the POLR3A mutation c.2554A>G (p.M852V) into human cell lines and assessed its impact on Pol III biogenesis, nuclear import, DNA occupancy, transcription, and protein levels. Transcriptomic profiling uncovered a subset of transcripts vulnerable to Pol III hypofunction, including a global reduction in tRNA levels. The brain cytoplasmic BC200 RNA (BCYRN1), involved in translation regulation, was consistently affected in all our cellular models, including patient-derived fibroblasts. Genomic BC200 deletion in an oligodendroglial cell line led to major transcriptomic and proteomic changes, having a larger impact than those of POLR3A mutations. Upon differentiation, mRNA levels of the MBP gene, encoding myelin basic protein, were significantly decreased in POLR3A-mutant cells. Our findings provide the first evidence for impaired Pol III transcription in cellular models of POLR3-HLD and identify several candidate effectors, including BC200 RNA, having a potential role in oligodendrocyte biology and involvement in the disease. Overall design: Gene expression profiling of Pol III transcripts in control and POLR3A-mutated cell lines (HEK293 and MO3.13) using RNA-seq and small RNA-seq; ChIP-seq of FLAG-tagged POLR3A-WT and mutated POLR3A-M852V
Leukodystrophy-associated <i>POLR3A</i> mutations down-regulate the RNA polymerase III transcript and important regulatory RNA <i>BC200</i>.
No sample metadata fields
View SamplesHigh-throughput transcriptomic (HTTr) technologies are increasingly being used to screen environmental chemicals in vitro to identify molecular targets and provide mechanistic context for regulatory testing. The androgen receptor (AR, NR3C4) regulates male sexual development, is involved in the pathogenesis of a number of cancers, and is often the target of endocrine disruptors. Here, we describe the development and validation of a novel gene expression biomarker to identify AR-modulating chemicals using a pattern matching method. AR biomarker genes were identified by their consistent expression after exposure to 4 AR agonists and opposite expression after exposure to 4 AR antagonists. A genetic filter was used to include only those genes that were regulated by AR. Most of the resulting 51 biomarker genes were shown to be directly regulated by AR as determined by ChIP-Seq analysis of AR-DNA interactions. The biomarker was evaluated as a predictive tool using the fold-change rank-based Running Fisher algorithm which compares the expression of AR biomarker genes under various treatment conditions. Using 163 comparisons from cells treated with 98 chemicals, the biomarker gave balanced accuracies for prediction of AR activation or AR suppression of 97% or 98%, respectively. The biomarker was able to correctly classify 16 out of 17 AR reference antagonists including those that are weak and very weak. Predictions based on comparisons from AR-positive LAPC-4 cells treated with 28 chemicals in antagonist mode were compared to those from an AR pathway model based on 11 in vitro high-throughput screening assays that queried different steps in AR signaling. The balanced accuracy was 93% for suppression. Using our approach, we identified conditions in which AR was modulated in a large collection of microarray profiles from prostate cancer cell lines including 1) AR constitutively active mutants or knockdown of AR, 2) depletion of androgens by castration or removal from media, and 3) modulators that work through indirect mechanisms including suppression of AR expression. These results demonstrate that the AR gene expression biomarker could be a useful tool in HTTr to identify AR modulators in large collections of microarray data derived from AR-positive prostate cancer cell lines.
Identification of Androgen Receptor Modulators in a Prostate Cancer Cell Line Microarray Compendium.
Specimen part, Cell line
View SamplesThis dataset details the time-dependent response of human Huh7 hepatoma cells to type I and type III IFN.
Dynamic expression profiling of type I and type III interferon-stimulated hepatocytes reveals a stable hierarchy of gene expression.
Cell line, Treatment, Time
View Samples