Identification of intrathymic Eomes+ natural Th1 cells creates a novel idea that there is more than one way for the generation of innate CD4 T cells. To more deeply characterize this type of innate T cells, we compared the gene expression profile between nTh1 cells generated in CIITAtg mice and classic Th1 cells differentiated from naive CD4 T cells in Th1-polarizing condition.
Thymic low affinity/avidity interaction selects natural Th1 cells.
Age, Specimen part
View SamplesN6-methyladenosine (m6A) is the most abundant internal modification of eukaryotic mRNA. This modification has previously been shown to alter the export kinetics for mRNAs though the molecular details surrounding this phenomenon remain poorly understood. Here we show that the m6A complex (WTAP, KIAA1429, METTL3/14) drives recruitment of the TREX mRNA export complex onto m6A modified mRNAs and this process is essential for the efficient export of certain mRNAs. Depletion of the core m6A complex leads to loss of TREX from mRNAs which undergo the m6A modification. We show that TREX stimulates recruitment of the m6A reader protein YTHDC1 to the mRNP and the m6A complex influences the interaction of TREX with YTHDC1. We suggest that m6A acts as a surrogate for other TREX recruitment mechanisms such as splicing and 5' capping, in long internal and final exons which may otherwise be devoid of this essential complex for mRNA export. Overall design: mRNA profiles of control and Virilizer/WTAP RNAi samples in cytoplasmic and nuclear cell fractions generated by mRNA-seq in triplicate using HiSeq 2500
The m<sup>6</sup>A-methylase complex recruits TREX and regulates mRNA export.
Cell line, Subject
View SamplesTerahertz (THz) technology has emerged for biomedical applications such as scanning, molecular spectroscopy, and medical imaging. However, the biological effect of THz radiation is not fully understood. Non-thermal effects of THz radiation were investigated by applying a femtosecond-terahertz (fs-THz) pulse to mouse skin. Analysis of the genome-wide expression profile in fs-THz-irradiated skin indicated that wound responses were predominantly through NFB1- and Smad3/4-mediated transcriptional activation. Repeated fs-THz radiation delayed the closure of mouse skin punch wounds due to up-regulation of transforming growth factor-beta (TGF-). These findings suggest that fs-THz radiation provokes a wound-like signal in skin with increased expression of TGF- and activation of its downstream target genes, which perturbs the wound healing process in vivo.
High-power femtosecond-terahertz pulse induces a wound response in mouse skin.
Sex, Specimen part
View SamplesTo determine the genes potentially responsible for the lactate-mediated gene expression regulation in hepatocellular carcinoma, we performed RNA-seq analyses on parental HepG2, HepG2/metR and oxamate-treated HepG2/metR cells. To gain mechanistic insights into the lactate-induced pro-migratory phenotypes, we established a cell model that acquired a resistance to metformin while producing lactate at a high level by selecting HepG2 cells that survived a chronic exposure to metformin for more than 5 months (HepG2/metR). In HepG2/metR cells, glycolysis rates were increased by more than 3 folds compared with parental cells, and consequently, lactate production was also highly enhanced. To clarify the gene expression regulation between the lactate level in the HepG2/metR model, we treated the cells with oxamate, an inhibitor of lactate dehydrogenase, and found that it significantly. Using a 2-fold change cut-off value in transcriptome, we selected 1,757 genes significantly up-regulated in HepG2/metR vs parental HepG2 cells. 690 genes were down-regulated by oxamate treatment in HepG2/metR cells. Eventually, we selected 136 genes that are common in the two gene sets, which may directly respond to lactate signaling Overall design: mRNA profiles of HepG2 cells, HepG2/metR (hyper-glycolytic cell model), oxamate treated HepG2/metR (decreased lactate concentration cell) were generated by deep sequencing using Illumina Nextseq 500
Lactate Activates the E2F Pathway to Promote Cell Motility by Up-Regulating Microtubule Modulating Genes.
Specimen part, Cell line, Treatment, Subject
View SamplesTime-course analysis of adipocyte gene expression profiles response to high fat diet. The hypothesis tested in the present study was that in diet-induced obesity, early activation of TLR-mediated inflammatory signaling cascades by CD antigen genes, leads to increased expression of pro-inflammatory cytokines and chemokines, resulting in chronic low-grade inflammation. Early changes in collagen genes may trigger the accumulation of ECM components, promoting fibrosis in the later stages of diet-induced obesity. New therapeutic approaches targeting visceral adipose tissue genes altered early by HFD feeding may help ameliorate the deleterious effects of a diet-induced obesity.
Time-course microarrays reveal early activation of the immune transcriptome and adipokine dysregulation leads to fibrosis in visceral adipose depots during diet-induced obesity.
Age, Specimen part, Treatment, Time
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Characterization of gene expression and activated signaling pathways in solid-pseudopapillary neoplasm of pancreas.
Sex, Age, Specimen part
View SamplesSolid-pseudopapillary neoplasm of pancreas(SPN), ductal adenocarcinoma(PCA), neuroendocrine tumor(NET) and non-neoplastic pancreas.
Characterization of gene expression and activated signaling pathways in solid-pseudopapillary neoplasm of pancreas.
Sex, Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Stability of gene expression and epigenetic profiles highlights the utility of patient-derived paediatric acute lymphoblastic leukaemia xenografts for investigating molecular mechanisms of drug resistance.
Sex
View SamplesThis series includes the global gene expression profile of the vastus lateralis muscle for 10 young (19-25 years old) and 12 older (70-80 years old) male subjects.
Identification of a molecular signature of sarcopenia.
No sample metadata fields
View SamplesBackground: Patient-derived tumour xenografts are an attractive model for preclinical testing of anti-cancer drugs. Insights into tumour biology and biomarkers predictive of responses to chemotherapeutic drugs can also be gained from investigating xenograft models. As a first step towards examining the equivalence of epigenetic profiles between xenografts and primary tumours in paediatric leukaemia, we performed genome-scale DNA methylation and gene expression profiling on a panel of 10 paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) tumours that were stratified by prednisolone response. Results: We found high correlations in DNA methylation and gene expression profiles between matching primary and xenograft tumour samples with Pearsons correlation coefficients ranging between 0.85 and 0.98. In order to demonstrate the potential utility of epigenetic analyses in BCPALL xenografts, we identified DNA methylation biomarkers that correlated with prednisolone responsiveness of the original tumour samples. Differential methylation of CAPS2, ARHGAP21, ARX and HOXB6 were confirmed by locus specific analysis. We identified 20 genes showing an inverse relationship between DNA methylation and gene expression in association with prednisolone response. Pathway analysis of these genes implicated apoptosis, cell signalling and cell structure networks in prednisolone responsiveness. Conclusions: The findings of this study confirm the stability of epigenetic and gene expression profiles of paediatric BCP-ALL propagated in mouse xenograft models. Further, our preliminary investigation of prednisolone sensitivity highlights the utility of mouse xenograft models for preclinical development of novel drug regimens with parallel investigation of underlying gene expression and epigenetic responses associated with novel drug responses.
Stability of gene expression and epigenetic profiles highlights the utility of patient-derived paediatric acute lymphoblastic leukaemia xenografts for investigating molecular mechanisms of drug resistance.
Sex
View Samples