Accumulated evidences suggest physiological relevance between the transcription factor NRF3 (NFE2L3) and cancers. However NRF3 target genes in cancer cells remain poorly understood.
Multiple regulatory mechanisms of the biological function of NRF3 (NFE2L3) control cancer cell proliferation.
Specimen part, Cell line
View SamplesPurpose: The purpose of the study was to investigate the differential expression pattern of genes in Rag2 KO mice spleen compared to its wild type counterpart.
Microarray profiling of miRNA and mRNA expression in Rag2 knockout and wild-type mouse spleens.
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Recombination activating gene-2<sup>null</sup> severe combined immunodeficient pigs and mice engraft human induced pluripotent stem cells differently.
Specimen part
View SamplesIt contains a disruption of the recombination activating gene 2 (RAG2) and homozygoue mice exhibit total inability to initiate V(D)J rearrangement and fail to generate mature T or B lymphocytes. (https://www.taconic.com)
Recombination activating gene-2<sup>null</sup> severe combined immunodeficient pigs and mice engraft human induced pluripotent stem cells differently.
Specimen part
View SamplesIt contains a disruption of the recombination activating gene 2 (RAG2) and homozygoue mice exhibit total inability to initiate V(D)J rearrangement and fail to generate mature T or B lymphocytes. (https://www.taconic.com)
Recombination activating gene-2<sup>null</sup> severe combined immunodeficient pigs and mice engraft human induced pluripotent stem cells differently.
Specimen part
View SamplesIt contains a disruption of the recombination activating gene 2 (RAG2) and homozygoue mice exhibit total inability to initiate V(D)J rearrangement and fail to generate mature T or B lymphocytes. (https://www.taconic.com)
Recombination activating gene-2<sup>null</sup> severe combined immunodeficient pigs and mice engraft human induced pluripotent stem cells differently.
Specimen part
View SamplesThis study aimed at investigating the impact of chronic ingestion of sebacic acid (SA), a 10 carbons medium-chain dicarboxylic acid, on glycemic control in a mouse model of type 2 diabetes (db/db mice). Three groups of 15 mice were fed for 6 weeks either a chow diet (Ctrl), or a chow diet supplemented with 1.5% or 15% (SA1.5% and SA15% resp.) energy from SA. Fasting glycemia was measured once a week and HbA1c before and after supplementation. An oral glucose tolerance test (OGTT) was performed at the end of the supplementation. Gene expression was determined by transcriptomic analysis on the liver of the Ctrl and SA15% groups. Results-After 42 days of supplementation, fasting glycemia and HbA1c were ~70% and ~25% lower in the SA15% group compared to other groups showing a beneficial effect of SA on hyperglycemia. During OGTT, blood glucose area under the curve (AUC) was reduced after SA15% compared to other groups. This effect was associated with a tendency for an improved insulin response. In the liver, Pck1 and FBP mRNA were statistically decreased in the SA15% compared to Ctrl suggesting a reduced hepatic glucose output induced by SA. Conclusions-Dietary supplementation of SA largely improves glycemic control in a mouse model of type 2 diabetes. This beneficial effect may be due (1) to a reduced hepatic glucose output resulting from transcriptional down regulation of key gluconeogenesis genes and (2) to an improved glucose induced-insulin secretion.
Six weeks' sebacic acid supplementation improves fasting plasma glucose, HbA1c and glucose tolerance in db/db mice.
Specimen part
View SamplesThe translation of novel pulmonary fibrosis therapies from preclinical models into the clinic represents a major challenge demonstrated by the high attrition rate of compounds that showed efficacy in preclinical models but demonstrated no significant beneficial effects in clinical trials. Precision-cut lung tissue slice (PCLS) contains all major cell types of the lung and preserves the original cell-cell and cell-matrix contacts. It represents a promising ex vivo model to study pulmonary fibrosis. In this study, using RNA sequencing, we demonstrated that TGFß1 induced robust fibrotic responses in the rat PCLS model as it changed the expression of genes functionally related to extracellular matrix remodeling, cell adhesion, epithelial-to-mesenchymal transition and various immune responses. Nintedanib, pirfenidone and sorafenib each reversed a subset of genes modulated by TGFß1 and of those genes we identified 229 genes whose expression was reversed by all three drugs. These genes define a molecular signature characterizing many aspects of pulmonary fibrosis pathology and its attenuation in the rat PCLS fibrosis model. A panel of 12 genes and 3 secreted biomarkers including procollagen I, HA and WISP1 were validated as efficacy endpoints for the evaluation of anti-fibrotic activity of experimental compounds. Finally, we showed that blockade of aV integrins suppressed TGFß1-induced fibrotic responses in the rat PCLS fibrosis model. Overall, our results suggest that the TGFß1-induced rat PCLS fibrosis model may represent a valuable system for target validation and to determine the efficacy of experimental compounds. Overall design: TGFb-treated rat precision-cut lung tissue slices (PCLS) were treated with drug and profiled with RNA-Seq
Molecular characterization of a precision-cut rat lung slice model for the evaluation of antifibrotic drugs.
Specimen part, Subject
View SamplesPrecision-cut liver tissue slice (PCLS) contains all major cell types of the liver parenchyma and preserves the original cell-cell and cell-matrix contacts. It represents a promising ex vivo model to study liver fibrosis and test the anti-fibrotic effect of experimental compounds in a physiologic environment. In this study using RNAquencing we demonstrated that various pathways functionally related to fibrotic mechanisms were dysregulated in PCLSs derived from rats subjected to bile duct ligation. The Alk5 inhibitor SB525334, nintedanib and sorafenib each reversed a subset of genes dysregulated in fibrotic PCLSs and of those genes we identified 608 genes whose expression was reversed by all three compounds. These genes define a molecular signature characterizing many aspects of liver fibrosis pathology and its attenuation in the model. A panel of 12 genes and 4 secreted biomarkers including procollagen I, HA, IGFBP5 and WISP1, were further validated as efficacy endpoints for the evaluation of anti-fibrotic activity of experimental compounds. Finally, we showed that blockade of aV integrins with a small molecule inhibitor attenuated the fibrotic phenotype in the model. Overall, our results suggest that the rat fibrotic PCLS model may represent a valuable system for target validation and to determine the efficacy of experimental compounds. Overall design: Precision-cut liver tissue slices (PCLS) from BDL rats were treated with drug and profiled with RNA-Seq
Molecular characterization of a precision-cut rat liver slice model for the evaluation of antifibrotic compounds.
Specimen part, Subject
View SamplesGenome-wide transcriptome analyses have allowed for systems- level insights into gene regulatory networks. Due to the limited depth of quantitative proteomics, however, our understanding of post-transcriptional gene regulation and its effects on protein complex stoichiometry are lagging behind. Here, we employ deep sequencing and iTRAQ technology to determine transcript and protein expression changes of a Drosophila brain tumour model at near genome-wide resolution. In total, we quantify more than 6,200 tissue-specific proteins, corresponding to about 70% of all transcribed protein-coding genes. Using our integrated data set, we demonstrate that post-transcriptional gene regulation varies considerably with biological function and is surprisingly high for genes regulating transcription. We combine our quantitative data with protein-protein interaction data and show that post-transcriptional mechanisms significantly enhance co-regulation of protein complex subunits beyond transcriptional co-regulation. Interestingly, our results suggest that only about 11% of the annotated Drosophila protein complexes are co-regulated in the brain. Finally, we refine the composition of some of these core protein complexes by analysing the co-regulation of potential subunits. Our comprehensive transcriptome and proteome data provide a rich resource for quantitative biology and offer novel insights into understanding post- transcriptional gene regulation in a tumour model. Overall design: Transcriptomes of 1-3 day old adult female Drosophila melanogaster heads of control and brat mutant were generated by deep sequencing, in triplicate, using Illumina GAIIx.
Transcriptome and proteome quantification of a tumor model provides novel insights into post-transcriptional gene regulation.
Subject
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