Expression profiles of 917 pathway repoter genes were determined by AmpliSeq-RNA in primary human hepatocytes treated with Diclofenac and a test compound 3 hours after treatment. Overall design: Vehicle control, diclofenac, and three doses of the test compound (small-molecule neurotransmitter receptor antagonist) were applied to three primary cell lines, with three biological replicates in each group. In some treatment groups read-outs were only available for two samples. All together 41 samples were profiled.
Pathway reporter genes define molecular phenotypes of human cells.
No sample metadata fieldsView Samples
Gene expression studies from hematopoietic stem cell (HSC) populations purified to variable degrees have defined a set of stemness genes. The present study describes the construction and comparative molecular analysis of l-phage cDNA libraries from highly purified primitive HSCs (PHSCs) which retained their long term repopulating activities (LTRAs), and from maturing HSCs (MHSCs) which were largely depleted of LTRAs. Library inserts were amplified and tagged by a T7 RNA polymerase promoter and used to generate biotinylated cRNA for Microarray hybridization. Microarray analysis of the libraries confirmed previous results but also revealed an unforseen preferential expression of translation and metabolism associated genes in the PHSCs. Therefore these data indicate that HSCs are quiescent only in regard of proliferative activities, but are in a state of readiness to provide the metabolic and translational activities required following induction of proliferation by factors which induce differentiation and exit from the HSC pool.
Gene expression profiles in murine hematopoietic stem cells revisited: analysis of cDNA libraries reveals high levels of translational and metabolic activities.
No sample metadata fieldsView Samples
A GFP-expressing recombinant A/Puerto Rico/8/1934 influenza virus was used to infect C57BL/6 wild type mice and on day 3 post infection, lung alveolar epithelial cells (AEC) were isolated and sorted based on GFP expression. GFP+ AEC represent the infected AEC and GFP- AEC represent the bystander AEC. AEC were also sorted from uninfected mice to serve as controls. Overall design: AEC from infected mice were pooled to make three (3) infected GFP+ AEC replicates for sequencing. Five (5) bystander GFP- replicates and five (5) uninfected AEC replicates were also isolated for sequencing
Transcriptome Analysis of Infected and Bystander Type 2 Alveolar Epithelial Cells during Influenza A Virus Infection Reveals <i>In Vivo</i> Wnt Pathway Downregulation.
Specimen part, Subject, TimeView Samples
We used microarrays to analyze gene expression changes in liver after treatment of rats with two compounds from drug development (R1, R2) to identify potential effects related to hepatotoxicity.
Gene expression-based in vivo and in vitro prediction of liver toxicity allows compound selection at an early stage of drug development.
Sex, Specimen part, TreatmentView Samples
There is increasing appreciation for sexually dimorphic effects, but the molecular mechanisms underlying these effects are only partially understood. In the present study, we explored transcriptomics and epigenetic differences in the small intestine and colon of prepubescent male and female mice. In addition, the microbiota composition of the colonic luminal content has been examined. At postnatal day 14, male and female C57BL/6 mice were sacrificed and the small intestine, colon and content of luminal colon were isolated. Gene expression of both segments of the intestine was analysed by microarray analysis. DNA methylation of the promoter regions of selected sexually dimorphic genes was examined by pyrosequencing. Composition of the microbiota was explored by deep sequencing. Sexually dimorphic genes were observed in both segments of the intestine of 2-week-old mouse pups, with a stronger effect in the small intestine. Amongst the total of 349 genes displaying a sexually dimorphic effect in the small intestine and/or colon, several candidates exhibited a previously established function in the intestine (i.e. Nts, Nucb2, Alox5ap and Retnl). In addition, differential expression of genes linked to intestinal bowel disease (i.e. Ccr3, Ccl11 and Tnfr) and colorectal cancer development (i.e. Wt1 and Mmp25) was observed between males and females. Amongst the genes displaying significant sexually dimorphic expression, nine genes were histone-modifying enzymes, suggesting that epigenetic mechanisms might be a potential underlying regulatory mechanism. However, our results reveal no significant changes in DNA methylation of analysed CpGs within the selected differentially expressed genes. With respect to the bacterial community composition in the colon, a dominant effect of litter origin was found but no significant sex effect was detected. However, a sex effect on the dominance of specific taxa was observed. This study reveals molecular dissimilarities between males and females in the small intestine and colon of prepubescent mice, which might underlie differences in physiological functioning and in disease predisposition in the two sexes.
Sexually dimorphic characteristics of the small intestine and colon of prepubescent C57BL/6 mice.
Sex, Age, Specimen partView Samples
MicroRNA-155 (miR-155) is upregulated in primary effector CD8 T cells but is expressed at low amounts in nave cells. Anti-viral CD8 T cell responses and viral clearance were impaired in miR-155 deficient (bic-/-) mice, and this defect was intrinsic to CD8 T cells, as adoptively transferred bic-/- CD8 T cells generated greatly reduced primary and memory responses during infection. To understand the mechanism by which miR-155 regulates CD8 T cell activation, we analyzed the gene expression profiles of naive and in vitro activated wild-type and bic-/- CD8 T cells.
The microRNA miR-155 controls CD8(+) T cell responses by regulating interferon signaling.
Specimen partView Samples
Although the prognosis for childhood Acute Lymphoblastic Leukemia (ALL) in general has improved tremendously over the last decades, the survival chances for infants (<1 year of age) with ALL remains poor.
Association of high-level MCL-1 expression with in vitro and in vivo prednisone resistance in MLL-rearranged infant acute lymphoblastic leukemia.
Sex, Specimen part, DiseaseView Samples
Hepatic lipid accumulation is an important complication of obesity linked to risk for type 2 diabetes. To identify novel transcriptional changes in human liver which could contribute to hepatic lipid accumulation and associated insulin resistance and type 2 diabetes (DM2), we evaluated gene expression and gene set enrichment in surgical liver biopsies from 13 obese (9 with DM2) and 5 control subjects, obtained in the fasting state at the time of elective abdominal surgery for obesity or cholecystectomy. RNA was isolated for cRNA preparation and hybridized to Affymetrix U133A microarrays.
Thyroid hormone-related regulation of gene expression in human fatty liver.
Sex, AgeView Samples
The transcription-related DNA damage response was analyzed on a genome-wide scale with great spatial and temporal resolution. Upon UV irradiation, a slowdown of transcript elongation and restriction of gene activity to the promoter-proximal ~25 kilobases is observed. This is associated with a shift from expression of long mRNAs to shorter isoforms, incorporating alternative last exons (ALEs) that are more proximal to the transcription start site. Notably, this includes a shift from a protein-coding ASCC3 mRNA to a shorter transcript isoform of which the RNA, rather than an encoded protein, is critical for the eventual recovery of transcription. The protein-coding ASCC3 isoform counteracts the function of the non-coding isoform, indicating crosstalk between them. Thus, the ASCC3 gene expresses both coding and noncoding transcript isoforms with opposite effects on transcription recovery after UV-induced DNA damage
UV Irradiation Induces a Non-coding RNA that Functionally Opposes the Protein Encoded by the Same Gene.
Cell line, Treatment, TimeView Samples