OSM increases the antiviral effect of IFN in Huh7 cells infected with hepatitis A virus (HAV) or HCV replicon and synergizes with IFN in the induction of antiviral genes
Oncostatin M enhances the antiviral effects of type I interferon and activates immunostimulatory functions in liver epithelial cells.
No sample metadata fields
View SamplesMultiple myeloma (MM) cells were treated with the BET inhibitor CPI203 alone and in combination with lenalidomide plus dexamethasone in vitro and in vivo (mouse xenograft).
The BET bromodomain inhibitor CPI203 improves lenalidomide and dexamethasone activity in <i>in vitro</i> and <i>in vivo</i> models of multiple myeloma by blockade of Ikaros and MYC signaling.
Specimen part, Cell line, Treatment
View SamplesHeterochromatin protein 1a (HP1a) is a chromatin associated protein that has been well studied in many model organisms, such as Drosophila, where it is a determining factor for classical heterochromatin. HP1a is associated with the two histone methyltransferases SETDB1 and Su(var)3-9, which mediate H3K9 methylation marks and participate in the establishment and spreading of HP1a enriched chromatin. While HP1a is generally regarded as a factor that represses gene transcription, several reports have linked HP1a binding to active genes, and in some cases, it has been shown to stimulate transcriptional activity. To clarify the function of HP1a in transcription regulation and its association with Su(var)3-9, SETDB1 and the chromosome 4 specific protein POF, we conducted genome-wide expression studies and combined the results with available binding data in Drosophila melanogaster. The results suggested that HP1a has a repressing function on chromosome 4, where it preferentially targets non-ubiquitously expressed genes (NUEGs), and a stimulating function in pericentromeric regions. Further, we showed that the effects of SETDB1 and Su(var)3-9 are similar to HP1a, and on chromosome 4, Su(var)3-9, SETDB1 and HP1a target the same genes. In contrast, transposons are repressed by HP1a and Su(var)3-9 but are un-affected by SETDB1 and POF. In addition, we found that the binding level and expression effects of HP1a are affected by gene length. Our results indicate that genes have adapted to be properly expressed in their local chromatin environment.
HP1a, Su(var)3-9, SETDB1 and POF stimulate or repress gene expression depending on genomic position, gene length and expression pattern in Drosophila melanogaster.
No sample metadata fields
View SamplesStudy of single and double mutants of the two roX RNAs in D. melanogaster Overall design: Study of single and double mutants of the two roX RNAs in D. melanogaster
RNA-on-X 1 and 2 in Drosophila melanogaster fulfill separate functions in dosage compensation.
Specimen part, Cell line, Subject
View SamplesThe aim was to identify genes that were commonly influenced by a siRNA targeting PRKCD in breast cancer cell lines.
Down Regulation of CLDND1 Induces Apoptosis in Breast Cancer Cells.
Cell line, Treatment
View SamplesHuman mesenchymal stem cells or multipotent stromal cells (MSCs) are of interest for clinical therapy, in part because of their capacity for proliferation and differentiation. However, results from clinical trials and in vitro models have been variable, possibly due to MSC heterogeneity and a lack of standardization between MSC in vitro expansion protocols. Here we defined changes in MSCs during expansion in vitro. In low density cultures, MSCs expand through distinct lag, exponential growth and stationary phases. We assayed cultures of passage 2 human MSCs from three donors at low density (50 cells/cm2) at about 5% confluence on Day 2 and after the cultures had expanded to about 70% confluence on Day 7. On Day 2 genes involved in cell division were up-regulated. On Day 7 genes for cell development were up-regulated. The variations between three donors were less than the variation within the expansion of MSCs from a single donor. The microarray data for selected genes were confirmed by real-time PCR, ELISA and FACScan. About 50% of cells at Day 2 were in S-phase compared to 10% at Day 7. The results demonstrated major differences in early and late stage cultures of MSCs that should be considered in using the cells in experiments and clinical applications.
Human multipotent stromal cells undergo sharp transition from division to development in culture.
No sample metadata fields
View SamplesIFN alpha mediated gene expression pattern. The effect of IFN alpha on human CD8 T cells responding to antigen (signal 1) and costimulatory signals (signal 2) provided by beads coated with anti-CD3 and anti-CD28 mAbs.
Effects of IFN-α as a signal-3 cytokine on human naïve and antigen-experienced CD8(+) T cells.
Specimen part, Subject, Time
View SamplesExpression profiling by high throughput sequencing Overall design: 23 Tumor samples were obtained from a Sleeping Beauty forward genetic screen and sequenced using Illumina HiSeq 2000
<i>Sleeping Beauty</i> Insertional Mutagenesis Reveals Important Genetic Drivers of Central Nervous System Embryonal Tumors.
Specimen part, Subject
View SamplesWe sought to obtain gene signature specific of high oxidative phsophorylation function.
Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism.
Cell line, Treatment
View SamplesIt has been hypothesized that chemotherapy resistant human acute myeloid leukemia (AML) cells are enriched in an immature phenotype, cellular quiescence and leukemic initiating cells (LICs). However, these hypotheses have never been validated completely in vivo. We have developed a physiologically relevant chemotherapeutic approach with cytosine arabinoside AraC using patient-derived xenograft (PDX) models. AraC-treated AML cells are not consistently enriched for either immature cells or quiescent cells. AraC treatment does not enrich for LICs as measured by limiting dilution in secondary transplantations. Rather chemotherapy resistant cells in vivo have high levels of reactive oxygen species (ROS) and a gene signature consistent with oxidative phosphorylation (OXPHOS). Treatment of human HIGH OXPHOS but not LOW OXPHOS AML cell lines showed chemotherapy resistance in vivo, showing that essential mitochondrial functions make significant contributions to AraC resistance in AML. Accordingly, targeting mitochondrial OXPHOS metabolism through the inhibition of mitochondrial protein synthesis, the electron transfer chain or fatty acid oxidation induced an energetic shift towards LOW OXPHOS and strongly enhanced anti-leukemic effects of AraC in AML cells. These results demonstrate that chemotherapy resistance in AML is not necessarily associated with stemness but is highly dependent on a distinct oxidative metabolism, and that the HIGH OXPHOS gene signature is a robust hallmark of the AraC response in PDX and a promising therapeutic avenue to treat AML residual disease.
Chemotherapy-Resistant Human Acute Myeloid Leukemia Cells Are Not Enriched for Leukemic Stem Cells but Require Oxidative Metabolism.
Specimen part, Disease
View Samples