The liver transcriptomes of two female groups (High and Low) with phenotypically extreme intramuscular fatty acid composition were sequenced using RNA-Seq [accn: SRA053452, subid: 86092, Bioproject: PRJNA168072]. A total of 146 and 180 unannotated protein-coding genes were identified in intergenic regions for the L and H groups, respectively. In addition, a range of 5.8 to 7.3% of repetitive elements was found, with SINEs being the most abundant elements. The expression in liver of 186 (L) and 270 (H) lncRNAs was also detected. The higher reproducibility of the RNA-Seq data was validated by RT-qPCR and porcine expression microarrays, therefore showing a strong correlation between RT-qPCR and RNA-Seq data (ranking from 0.79 to 0.96), as well as between microarrays and RNA-Seq (r=0.72). A differential expression analysis between H and L animals identified 55 genes differentially-expressed between groups. Pathways analysis revealed that these genes belong to biological functions, canonical pathways and three gene networks related to lipid and fatty acid metabolism. In concordance with the phenotypic classification, the pathways analysis inferred that linolenic and arachidonic acids metabolism was altered between extreme individuals. In addition, a connection was observed among the top three networks, hence suggesting that these genes are interconnected and play an important role in lipid and fatty acid metabolism.
Liver transcriptome profile in pigs with extreme phenotypes of intramuscular fatty acid composition.
Sex, Specimen part
View SamplesVery little is known about how animals discriminate pathogens from innocuous microbes. To address this question, we examined infection-response gene induction in the nematode Caenorhabditis elegans. We focused on genes that are induced in C. elegans by infection with the bacterial pathogen Pseudomonas aeruginosa, but are not induced by an isogenic attenuated gacA mutant. Most of these genes are induced independently of known immunity pathways. We generated a GFP reporter for one of these genes, infection response gene 1 (irg-1), which is induced strongly by wild-type P. aeruginosa strain PA14, but not by other C. elegans pathogens or by other wild-type P. aeruginosa strains that are weakly pathogenic to C. elegans. To identify components of the pathway that induces irg-1 in response to infection, we performed an RNA interference screen of C. elegans transcription factors. This screen identified zip-2, a bZIP transcription factor that is required for inducing irg-1, as well as several other genes, and is important for defense against infection by P. aeruginosa. These data indicate that zip-2 is part of a specialized pathogen response pathway that is induced by virulent strains of P. aeruginosa and provides defense against this pathogen.
bZIP transcription factor zip-2 mediates an early response to Pseudomonas aeruginosa infection in Caenorhabditis elegans.
Time
View SamplesMetastasis is a complex process involving loss of adhesion, migration, invasion and proliferation of cancer cells. Cell adhesion molecules play a pivotal role in this phenomenon by regulating cell-cell and cell-matrix interactions. CD146 (MCAM) is associated with advanced tumor stage in melanoma, prostate and ovarian cancers.
CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines.
No sample metadata fields
View SamplesGene expression of T47D-MTVL human breast cancer cells expressing Dox-inducible shRNAs against histone H1.4 (120sh) or multiple H1 variants (225sh) Overall design: Stable breast cancer-derived cell lines expressing an shRNA against one of each of the histone H1 isoforms in response to doxycycline (Dox) were grown for six days in the presence or absence of Doxicycline, RNA extracted and high-thorughput sequenced. Cell lines used: inducible shRNA against H1.4 or multiple H1 variants and random shRNA-expression vector.
Histone H1 depletion triggers an interferon response in cancer cells via activation of heterochromatic repeats.
Cell line, Subject
View SamplesIn this study we tested the ability to predict organ injury from transcriptomics data in Sprague-Dawley rats at early time points after exposure to thioacetmide (8 and 24 hours). We selected thioacetamide, an organosulfur compound extensively used in animal studies as a hepatotoxin and carcinogen for its ability to cause acute liver damage. Overall design: We treated 30 Sprague-Dawley rats with saline solution (control), 25 mg/kg (low dose), and 100 mg/kg (high dose) to produce different degrees of injury. RNA samples for gene expression analysis were collected from the liver, kidney, and heart at 8 and 24 hours. Number of repicates were five.
Concordance between Thioacetamide-Induced Liver Injury in Rat and Human In Vitro Gene Expression Data.
Specimen part, Cell line, Subject
View SamplesMouse ESCs depleted of the epigenetic modifying enzyme Usp22 fail to differentiate properly. Ectopic expresison of Usp22 results in spontaneous differnetiation.
The epigenetic modifier ubiquitin-specific protease 22 (USP22) regulates embryonic stem cell differentiation via transcriptional repression of sex-determining region Y-box 2 (SOX2).
Cell line, Treatment
View SamplesDiffering from other experimental models, intranasal infection with vaccine strain of Venezuelan equine encephalitis virus, VEEV, (TC83) caused high titer infection in the brain and 90100% mortality in the C3H/HeN murine model. Intranasal infection with VEEV (TC83) caused persistent viral infection in the brains of mice without functional T-cells (-TCR -/-). While wild-type C57BL/6 mice clear infectious virus in the brain by 13 dpi, -TCR -/- maintain infectious virus in the brain to 92 dpi.
Natural killer cell mediated pathogenesis determines outcome of central nervous system infection with Venezuelan equine encephalitis virus in C3H/HeN mice.
Sex, Specimen part
View SamplesFull title: Genome-wide expression profiles of primary human small airway epithelial cells (SAECs) infected with different adenovirus mutants.
Heterochromatin silencing of p53 target genes by a small viral protein.
Specimen part
View SamplesMedullary breast cancers (MBC) display a basal profile, but a favorable prognosis. We hypothesized that a previously published 368-gene expression signature associated with MBC might serve to define a prognostic classifier in basal cancers. We collected public gene expression and histoclinical data of 2145 invasive early breast adenocarcinomas. We developed a Support Vector Machine (SVM) classifier based on this 368-gene list in a learning set, and tested its predictive performances in an independent validation set. Then, we assessed its prognostic value and that of six prognostic signatures for disease-free survival (DFS) in the remaining 2034 samples. The SVM model accurately classified all MBC samples in the learning and validation sets. A total of 466 cases were basal across other sets. The SVM classifier separated them into two subgroups, subgroup 1 (resembling MBC) and subgroup 2 (not resembling MBC). Subgroup 1 exhibited 71% 5-year DFS, whereas subgroup 2 exhibited 50% (p=9.93E-05). The classifier outperformed the classical prognostic variables in multivariate analysis, conferring lesser risk for relapse in subgroup 1 (HR=0.52, p=3.9E-04). This prognostic value was specific to the basal subtype, in which none of the other prognostic signatures was informative.
A gene expression signature identifies two prognostic subgroups of basal breast cancer.
Age, Specimen part
View SamplesDirect conversion of fibroblasts to induced cardiomyocytes (iCMs) has great potential for regenerative medicine. Recent publications have reported significant progress, but the evaluation of reprogramming has relied upon non-functional measures such as flow cytometry for cardiomyocyte markers or GFP expression driven by a cardiomyocyte-specific promoter. The issue is one of practicality: the most stringent measures - electrophysiology to detect cell excitation and the presence of spontaneously contracting myocytes - are not readily quantifiable in the large numbers of cells screened in reprogramming experiments. However, excitation and contraction are linked by a third functional characteristic of cardiomyocytes: the rhythmic oscillation of intracellular calcium levels. We set out to optimize direct conversion of fibroblasts to iCMs with a quantifiable calcium reporter to rapidly assess functional transdifferentiation. We constructed a reporter system in which the calcium indicator GCaMP is driven by the cardiomyocyte-specific Troponin T promoter. Using calcium activity as our primary outcome measure, we compared several published combinations of transcription factors along with novel combinations in mouse embryonic fibroblasts. The most effective combination consisted of Hand2, Nkx2.5, Gata4, Mef2c, and Tbx5 (HNGMT). This combination is >50-fold more efficient than GMT alone and produces iCMs with cardiomyocyte marker expression, robust calcium oscillation, and spontaneous beating that persists for weeks following inactivation of reprogramming factors. HNGMT is also significantly more effective than previously published factor combinations for the transdifferentiation of adult mouse cardiac fibroblasts to iCMs. Quantification of calcium function is a convenient and effective means for the identification and evaluation of cardiomyocytes generated by direct reprogramming. Using this stringent outcome measure, we conclude that HNGMT produces iCMs more efficiently than previously published methods.
Optimization of direct fibroblast reprogramming to cardiomyocytes using calcium activity as a functional measure of success.
No sample metadata fields
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