Knowing the gene expression profiles of drug-metabolizing enzymes and transporters throughout gestation is important for understanding the mechanisms of pregnancy-induced changes in drug pharmacokinetics. In this study, we compared gene expression of drug-metabolizing enzymes and transporters in the maternal liver, kidney, small intestine, and placenta of pregnant mice throughout gestation by microarray analysis. Specifically, we investigated cytochrome P450 (Cyp), UDP-glucuronosyltranserase (Ugt), and sulfotransferase (Sult), as well as ATP-binding cassette (Abc) and solute carrier (Slc) transporters. We found that relatively few Ugt and Sult genes were impacted by pregnancy in maternal tissues and placenta. Cyp1a2, most Cyp2 isoforms, Cyp3a11, and Cyp3a13 in the liver were down-regulated, with the greatest changes occurring on gestation days (gd) 15 and 19 compared to non-pregnant controls (gd 0). However, Cyp2d40, Cyp3a16, Cyp3a41a, Cyp3a41b, and Cyp3a44 in the liver were induced throughout pregnancy. Cyp expression in mid-gestation placenta (gd 10 and 15) was generally greater than that in term placenta (gd 19). There were also notable changes in Abc and Slc transporters. Abcc3 in the liver was down-regulated by 60%, and Abcb1a, Abcc4, and Slco4c1 in the kidney were down-regulated by 30-60% on gd 15 and 19 versus gd 0. Abcc5 in the placenta was induced 3-fold on gd 10 versus gd 15 and 19, whereas Slc22a3 expression in the placenta on gd 10 was 90% lower than that on gd 15 and 19. Overall, this study demonstrates important gestational age-dependent expression of drug-metabolizing enzymes and transporter genes, which may have mechanistic relevance to human pregnancy.
Gestational age-dependent changes in gene expression of metabolic enzymes and transporters in pregnant mice.
Specimen part
View SamplesThe specific genes that influence neuroblastoma biology and are targeted by genomic alterations remain largely unknown. We quantified mRNA expression in a highly annotated series of 101 prospectively collected diagnostic neuroblastoma primary tumors and the expression profiles were determined using Affymetrix U95Av2 arrays. Comparisons between the sample groups allow the identification of genes with localized expression patterns. This study demonstrates that the genomic data can be used to subcategorize the disease into molecular subsets and the regional copy number alterations are correlated with a broad number of transcriptional alterations genome wide. This data also suggests that multiple genes from several discrete regions of the human genome co-operate to supress neuroblastoma tumorigenesis and progression.
Integrative genomics identifies distinct molecular classes of neuroblastoma and shows that multiple genes are targeted by regional alterations in DNA copy number.
No sample metadata fields
View SamplesThe goal of this study was to investigate the role of intragenic CTCF in alternative pre-mRNA splicing through a combined CTCF-ChIP-seq and RNA-seq approach. CTCF depletion led to decreased inclusion of weak upstream exons. Overall design: CTCF ChIP-seq was performed in BJAB and BL41 B cell lines and normalized relative to Rabbit Ig control IP-seq reads. RNA-seq was performed in BJAB and BL41 cells transduced with shRNA against CTCF or RFP as a control, and in untransduced cells as well.
CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing.
Cell line, Subject
View SamplesCyclic AMP response element binding protein (CREB) is known to play important roles in growth and drug resistance of various cancers. Here we show roles of inhibition of CREB1 on gene expression profile of malignant mesothelioma (MM) cells (Hmeso and H2373/PPMMill).
CREB-induced inflammation is important for malignant mesothelioma growth.
Cell line
View SamplesPhosphorus is an essential macronutrient element, but some time causes problems if present in excess. Unlike the enormous molecular and morphophysiological information available in plants regarding phosphate (Pi) deficiency, little is known about the effect of excess Pi on plants, which is indeed essential for its remediation. Here, we have carried out a comparative study of plant molecular responses under excess Pi (20 mM) or without Pi (0 mM) at transcriptome level. The 1.25 mM treatment concentration of Pi used as a control to obtain differentially regulated genes under above mentioned Pi regimes. A novel whole-transcript expression array, i.e. Arabidopsis Gene 1.0 ST Array, was used to perform these experiments. The most distinctly regulated groups of genes represent modulation in ethylene mediated signaling, Fe deficiency response, and root development. We have also identified some defensin like genes, possessing a gibberellic acid regulated domain (GASA like) under excess Pi treatment. Overall, this study will not only help in dissecting the mechanism of plant responses under excess Pi but also provide the clues about the unknown genes involved in phosphorus homeostasis.
Comprehensive study of excess phosphate response reveals ethylene mediated signaling that negatively regulates plant growth and development.
Specimen part
View SamplesGenome-wide transcriptome analysis was carried out in root tissue of Arabidopsis seedlings treated with gold (Au) as Chloroauric acid (HAuCl4). This study demonstrated remarkable changes in root transcriptome within the 12 h exposure. Most of the genes differentially expressed were related to glutathione binding, methylations, secondary metabolism, sugar metabolism, ABA, ethylene, auxin related signalling, transport and signal-transduction pathways.
Genome wide transcriptome analysis reveals ABA mediated response in Arabidopsis during gold (AuCl(-) 4) treatment.
Specimen part, Treatment
View SamplesN1-Methyladenosine (m1A) is a prevalent post-transcriptional RNA modification, yet little is known about its abundance, topol- ogy and dynamics in mRNA. Here, we show that m1A is prevalent in Homo sapiens mRNA, which shows an m1A/A ratio of ~0.02%. We develop the m1A-ID-seq technique, based on m1A immunoprecipitation and the inherent ability of m1A to stall reverse tran- scription, as a means for transcriptome-wide m1A profiling. m1A-ID-seq identifies 901 m1A peaks (from 600 genes) in mRNA and noncoding RNA and reveals a prominent feature, enrichment in the 5'' untranslated region of mRNA transcripts, that is dis- tinct from the pattern for N6-methyladenosine, the most abundant internal mammalian mRNA modification. Moreover, m1A in mRNA is reversible by ALKBH3, a known DNA/RNA demethylase. Lastly, we show that m1A methylation responds dynamically to stimuli, and we identify hundreds of stress-induced m1A sites. Collectively, our approaches allow comprehensive analysis of m1A modification and provide tools for functional studies of potential epigenetic regulation via the reversible and dynamic m1A methylation. Overall design: Identification of m1A sites in human embryonic kidney cells. Comparisons of m1A profiles of wild type HEK293T with ALKBH3 knock out cell line reveals the ALKBH3 specific sites. Stress inducible m1A sites are also identified by comparing the profiles of untreated cells with stress treated cells.
Transcriptome-wide mapping reveals reversible and dynamic N(1)-methyladenosine methylome.
No sample metadata fields
View SamplesWe hypothesize that the observed differences in incidences of pleural and peritoneal malignant mesothelioma (MM) are the result of differences in the direct response of these cell types to asbestos rather than to differences mediated by the in vivo microenvironment. To test this hypothesis, we characterized cellular responses to asbestos in a controlled environment using high-throughput RNA sequence and other assays. Overall design: Examination of asbestos-treated versus untreated mesothelial cells from four cell lines representing two tissue types in culture.
Differential Susceptibility of Human Pleural and Peritoneal Mesothelial Cells to Asbestos Exposure.
No sample metadata fields
View SamplesPurpose: Single cell RNA-seq could observe heterogeneity of cell transcriptomes. The goals of this study are to compare the changes of ESCC cell line KYSE-180 RNA profiles in response to different doses of radiotherapy and to analyze the radio-resistance related genes. Overall design: Methods: Cultured KYSE-180 cells accepted accumulative irradiation doses of 0 Gy, 12 Gy or 30 Gy, respectively. Single cell libraries were generated by Smart-seq 2 kit, sequenced using Illumina HiSeq 2500. The sequence reads that passed quality filters were analyzed at the transcript expression level with TopHat followed by DESeq2/Monocle.
Population and single‑cell transcriptome analyses reveal diverse transcriptional changes associated with radioresistance in esophageal squamous cell carcinoma.
Specimen part, Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Altered expression of the Cdk5 activator-like protein, Cdk5α, causes neurodegeneration, in part by accelerating the rate of aging.
Sex, Age, Specimen part
View Samples