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SRP034938
Gallus gallus
1 Downloadable Sample
Illumina HiSeq 2000
Description
Marek’s disease virus 1 (MDV-1), an oncogenic -herpesvirus that induces T-cell lymphomas in chickens, serves as model system to study transformation by lymphotropic herpesviruses. Like the oncogenic human -herpesviruses Kaposi’s sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV), MDV-1 encodes several viral microRNAs (miRNAs). One MDV-1 miRNA, miR-M4, shares the same “seed” targeting sequence with both a KSHV miRNA, miR-K11, and cellular miR-155. Importantly, miR-M4 plays a critical role in T-cell transformation by MDV-1, while miR-K11 and cellular miR-155 are thought to play key roles in B-cell transformation by KSHV and EBV, respectively. Here, we present an analysis of the mRNAs targeted by viral miRNAs expressed in the chicken T-cell line MSB1, which is naturally coinfected with MDV-1 and the related nonpathogenic virus MDV-2. Our analysis identified>1,000 endogenous mRNAs targeted by miRNAs encoded by each virus, many of which are targeted by both MDV-1 and MDV-2 miRNAs. We present a functional analysis of an MDV-1 gene, RLORF8, targeted by four MDV-1 miRNAs and a cellular gene, encoding interleukin-18 (IL-18) and targeted by both MDV-1 and MDV-2 miRNAs, and show that ectopic expression of either protein in a form resistant to miRNA inhibition results in inhibition of cell proliferation. Finally, we present a restricted list of 9 genes targeted by not only MDV-1 miR-M4 but also KSHV miR-K11 and human miR-155. Given the critical role played by miR-155 seed family members in lymphomagenesis in humans and chickens, these mRNA targets may contain genes whose inhibition plays a conserved role in herpesvirus transformation. Overall design: PAR-CLIP experiment of MSB1 cells
Publication Title
Analysis of the mRNA targetome of microRNAs expressed by Marek's disease virus.
Sample Metadata Fields
Specimen part, Cell line, Subject
View Samples- Mus musculus
- 4 Downloadable Samples
Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
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.
Publication Title
Thymic low affinity/avidity interaction selects natural Th1 cells.
Sample Metadata Fields
Age, Specimen part
View Samples- Mus musculus
- 656 Downloadable Samples
- IlluminaHiSeq2500
Description
We introduced genome-wide pooled CRISPR-Cas9 libraries into primary mouse dendritic cells (DCs) to identify genes that control the induction of tumor necrosis factor (TNF) by bacterial lipopolysaccharide (LPS), a key process in the host response to pathogens, mediated by the TLR4 pathway. We found many of the known regulators of TLR4 signaling, as well as dozens of previously unknown candidates that we validated. Overall design: We used stain base phenotype (staining for TNF) in order to search for negative and positive regulators of LPS response in differentiated BMDCs
Publication Title
A Genome-wide CRISPR Screen in Primary Immune Cells to Dissect Regulatory Networks.
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 33 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
Pancreatic islet transplantation as a cure for type 1 diabetes (T1D) cannot be scaled up due to a scarcity of human pancreas donors. In vitro expansion of beta cells from mature human pancreatic islets provides an alternative source of insulin-producing cells. The exact nature of the expanded cells produced by diverse expansion protocols, and their potential for differentiation into functional beta cells, remain elusive. We performed a large-scale meta-analysis of gene expression in human pancreatic islet cells, which were processed using three different previously described protocols for expansion and attempted re-differentiation. All three expansion protocols induced dramatic changes in the expression profiles of pancreatic islets; many of these changes are shared among the three protocols. Attempts at re-differentiation of expanded cells induce a limited number of gene expression changes. Nevertheless, these fail to restore a pancreatic islet-like gene expression pattern. Comparison with a collection of public microarray datasets confirmed that expanded cells are highly comparable to mesenchymal stem cells. Genes induced in expanded cells are also enriched for targets of transcription factors important for pluripotency induction. The present data increases our understanding of the active pathways in expanded and re-differentiated islets. Knowledge of the mesenchymal stem cell potential may help development of drug therapeutics to restore beta cell mass in T1D patients.
Publication Title
Meta-analysis of gene expression in human pancreatic islets after in vitro expansion.
Sample Metadata Fields
Specimen part
View Samples- Rattus norvegicus
- 6 Downloadable Samples
- Affymetrix Rat Gene 1.0 ST Array (ragene10st)
Description
We found that in rodents, b-cell mass expansion during pregnancy and obesity is associated with changes in the expression of a group of islet microRNAs. We were able to reproduce in isolated pancreatic islets the decrease of miR-338-3p level observed in gestation and obesity by activating the G-protein coupled estrogen receptor GPR30 and the GLP1 receptor. Blockade of miR-338-3p in b-cells using specific anti-miR molecules mimicked gene expression changes occurring during b-cell mass expansion and resulted in increased proliferation and improved survival both in vitro and in vivo. These findings point to a major role for miR-338-3p in compensatory b-cell mass expansion occurring under different insulin resistance states.
Publication Title
MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity.
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Mus musculus
- 6 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Terahertz (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.
Publication Title
High-power femtosecond-terahertz pulse induces a wound response in mouse skin.
Sample Metadata Fields
Sex, Specimen part
View Samples- Saccharomyces cerevisiae
- 15 Downloadable Samples
- Illumina HiSeq 2000
Description
Histone H3K4 methylation is connected to gene transcription from yeast to humans, but its mechanistic role in transcription and chromatin dynamics remains poorly understood. Here, we investigated the functions for Set1 and Jhd2, the sole H3K4 methyltransferase and H3K4 demethylase, respectively, in S. cerevisiae. Our data show that Set1 and Jhd2 predominantly co-regulate transcription. To further understand the role for H3K4 methylation, we overexpressed Flag epitope-tagged SET1-G990E (a dominant hyperactive allele of SET1) in yeast using the constitutive ADH1 promoter (ADH1p). As a control, we also overexpressed Flag epitope-tagged wild type SET1 in yeast. Analysis of gene expression in set1-null, jhd2-null and wild type SET1 or hypeactive SET1-G990E overexpressing mutants together revealed that the transcriptional regulation at a sub-set of genes, inclduing those governing glycogen metabolism and ribosome biogenesis, is highly sensitive to any change (i.e., loss or gain) in H3K4 methylation levels. Overall, we find combined activities of Set1 and Jhd2 via dynamic modulation of H3K4 methylation contribute to positive or negative transcriptional regulation at shared target genes. Overall design: Gene expression changes were generated from five different yeast strains representing wild type control, set1 null and jhd2 null mutants, and wild type SET1 or dominant hyperacive SET1-G990E overexpressing mutants. Three independent biological samples were grown for each strain, total RNA was isolated, libraries were prepared, sequenced, and analyzed separately.
Publication Title
Counteracting H3K4 methylation modulators Set1 and Jhd2 co-regulate chromatin dynamics and gene transcription.
Sample Metadata Fields
Cell line, Subject
View Samples- Homo sapiens
- 3 Downloadable Samples
- NextSeq 500
Description
To 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
Publication Title
Lactate Activates the E2F Pathway to Promote Cell Motility by Up-Regulating Microtubule Modulating Genes.
Sample Metadata Fields
Specimen part, Cell line, Treatment, Subject
View Samples- Drosophila melanogaster
- 8 Downloadable Samples
- Illumina HiSeq 2000
Description
We 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)
Publication Title
Population- and sex-biased gene expression in the excretion organs of Drosophila melanogaster.
Sample Metadata Fields
Sex, Subject
View Samples- Mus musculus
- 91 Downloadable Samples
- Illumina MouseWG-6 v2.0 expression beadchip
Description
Time-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.
Publication Title
Time-course microarrays reveal early activation of the immune transcriptome and adipokine dysregulation leads to fibrosis in visceral adipose depots during diet-induced obesity.
Sample Metadata Fields
Age, Specimen part, Treatment, Time
View Samples