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 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 SamplesPhosphorylation of histone H3 at Serine 10 emerges as a mechanism increasing chromatin accessibility of the transcription factor NF-kB for a particular set of immune genes. Here we report that a bacterial pathogen uses this strategy to shape the transcriptional response of infected host cells. We identify the Shigella flexneri type III protein effector OspF as a Dual Specific Phosphatase. OspF dephosphorylates MAP kinases within the nucleus impairing histone H3 phosphorylation at Serine 10 in a gene-specific manner. Therefore, OspF reprograms the transcriptional response for inactivation of a subset of NF-kB responsive genes. This regulation leads to repression of polymorphonuclear leukocytes recruitment in infected tissues. Thus, pathogens have evolved the ability to precisely modulate host cell epigenetic information as a strategy to repress innate immunity.
An injected bacterial effector targets chromatin access for transcription factor NF-kappaB to alter transcription of host genes involved in immune responses.
No sample metadata fields
View SamplesHere, we examined the host response relative of SACC-PHHs infected with either hepatitis B virus (HBV) alone or both HBV/hepatitis delta virus (HDV) co-infection compared to non-infected controls. Overall design: SACC-PHHs were generated with PHHs from either a single human donor or mixed donors (in total, there were five donors) and co-cultured with 3T3J mouse non-parenchymal cells. These cultures can be persistently infected for up to 1-1.5 months post-challenge and exhibit a transcriptomic profile similar to what's observed in the 3D context of the liver. Note that not all donors and conditions have the same number of replicates.
Analysis of Host Responses to Hepatitis B and Delta Viral Infections in a Micro-scalable Hepatic Co-culture System.
Specimen part, Treatment, Subject
View SamplesWe previously identified the induction of growth arrest with phenotypic characteristics of senescence in melanoma cell lines sensitive to diterpene esters, indicating a therapeutic potential. Here we compared the cytostatic effects of two diterpene esters namely TPA (12-O-tetradecanoylphorbol-13-acetate) and PEP008 (20-O-acetyl-ingenol-3-angelate) in sensitive and resistant cell lines derived from melanoma, breast cancer and colon cancer. We showed the diterpene esters to induce senescence-like growth arrest in the sensitive cells at 100-1000 ng/ml. Use of the pan-PKC inhibitor bisindolylmaleimide-l demonstrated that activation of PKC was required for growth arrest. Full genome expression profiling revealed that pivotal genes involved in DNA synthesis and cell cycle control were down-regulated by treatment in all three sensitive solid tumor models. At the protein level, prolonged down-regulation of E2F-1 and proliferating cell nuclear antigen (PCNA), sustained expression of p21WAF1/CIP1 and dephosphorylation of retinoblastoma (Rb) occurred in the sensitive cells. Although activation of extracellular signal-related kinase (ERK) 1/2 by the diterpene esters occurred in both sensitive and resistant cell lines, the HRASLS3 type II tumor suppressor, which appears to have a role in MAPK pathway suppression, was constitutively elevated in the resistant cell lines compared to their sensitive counterparts. Together, these results demonstrate the ability of the PKC activating drugs TPA and PEP008 to induce growth arrest with characteristics of senescence in solid tumor cell lines derived from a variety of tissue types through a similar mechanism. PKC-activating diterpene esters may therefore have therapeutic potential in a range of solid tumors.
Induction of senescence in diterpene ester-treated melanoma cells via protein kinase C-dependent hyperactivation of the mitogen-activated protein kinase pathway.
No sample metadata fields
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 SamplesWe used RNA-seq to investigate gene expression variation in Malpighian tubules, which have a function analogous to that of human kidneys. In order to characterize population differentiation, we sequenced the Malpighian tubule transcriptomes of flies derived from two populations, one from sub-Saharan Africa (Zimbabwe) and one from Europe (the Netherlands). Males and females were examined separately. Overall, we found a high amount of differential expression between sexes (2,308 genes) and populations (2,474 genes). Although most of the differentially expressed genes were consistent between sexes and populations, there were 615 genes showed sex-biased expression in only one population and 557 genes showed population-biased expression in only one sex. Overall design: mRNA expression profiles of Drosophila melanogaster Malpighian tubules from adult males and females from a European and an African population (2 biological replicates per sex and population)
Population- and sex-biased gene expression in the excretion organs of Drosophila melanogaster.
Sex, 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 Samples