Transcriptome analysis of human primary fibroblasts treated with 250µM HU versus untreated primary fibroblats
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Bernard Lopez
PROVIDER: E-MTAB-8605 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Overexpression of miR-181a in AML blasts: DNA Microarray was performed to compare overall gene expression profiles of KG-1 Anti-miR-CT and U937 Anti-miR-CT cells compared respectively to KG-1 Anti-miR-181a and U937 Anti-miR-181a.
2014-12-30 | E-MTAB-2837 | biostudies-arrayexpress
Project description:We have previously shown that human umbilical cord blood CD34+ progenitor cells undergo in vitro differentiation into functional NK cells and that their co-culture in the presence of HOXB4 transduced stromal MS5 cells resulted in an increase in differentiated NK number. The present study was conducted to compare the stromal effect on NK lytic potential in the presence and absence of HOXB4. Our results provide evidence that HOXB4 transduced MS5 cells as compared to transduced, GFP (+) MS5 cells induced highly differentiated cytotoxic NK cells. Importantly, this difference was not due to the expression of activating NK receptors but was associated with an increased induction of granzyme B degranulation in response to stimulation with NK cell-susceptible targets. DNA microarray-based global transcriptional profiling confirmed the up-regulation of granzyme B. These findings provide further evidence that HOXB4 is a crucial regulator of NK function and that its use in generating functional NK cells with increased lytic potential may be significant for cancer immunotherapy.
2014-06-07 | E-MTAB-1710 | biostudies-arrayexpress
Project description:Targeting the reprogramming and phagocytic capacities of tumor-associated macrophages (TAMs) has emerged as a therapeutic opportunity for cancer treatment. Here, we demonstrate that leukemic cell phagocytosis triggers the proinflammatory activation of TAMs as demonstrated by the upregulation and dowregulation of, respectively, proinflammatory and anti-inflammatory genes in phagocytic macrophages (Phago+) with respect to non-phagocytic macrophages (Phago-).
2022-10-25 | E-MTAB-12280 | biostudies-arrayexpress
Project description:The aim of the present study was to investigate the potential role of HIF-2a in regulating RCC susceptibility to natural killer (NK) cell-mediated killing. We demonstrated that the RCC cell line 786-O with mutated VHL was resistant to NK-mediated lysis as compared to the VHL corrected cell line (WT7). This resistance was independent of immunological synapse formation and NK ligand expression but was found to be reliant on HIF-2a stabilization in 786-0 cells. In order to elucidate the molecular basis of HIF-2a-induced impairment of NK-mediated killing, we performed global gene analysis using DNA microarray. Three candidate genes (ANGPTL4, ADM and ITPR1) were selected on the basis of their fold change and their involvement in cell death and survival. SiRNA targeting of these genes revealed that only ITPR1 silencing resulted in a significant increase of 786-O susceptibility to NK-mediated lysis. Using gene silencing of HIF2-a and chromatin immunoprecipitation assay, we showed for the first time that ITPR1 was a direct novel target of HIF2-a. Notably, a strong and significant correlation was found between ITPR1and HIF2-a staining in RCC patients. Transcriptional profiling of ITPR1silenced RCC cells indicated that several important genes involved in cell survival and apoptosis were differentially regulated. Using ITPR1 silenced Renca cells, we further found that ITPR1 was involved in the control of tumor progression. Moreover ITPR1 targeting combined with NK depletion significantly enhanced tumor growth as compared to ITPR1 knocked down Renca xenografts. Our data provide insights into the link between HIF-2a, ITPR1-related pathway and natural immunity and suggest a role of the HIF2/ITPR1 axis in regulating RCC cell survival.
2014-01-11 | E-MTAB-1802 | biostudies-arrayexpress
Project description:To understand ta-siRNA-mediated regulation network in response to abiotic stress during flower development, gene expression profiles of flowering buds between rdr6-15 and wild-type under moderate drought stress and control condition were measured using microarray. 512 genes were bilaterally regulated by drought stress signal and RDR6-mediated signal. rdr6-15 and wild-type plants (Arabidopsis thaliana ecotype Columbia) were grown on 30g of vermiculite soil of plastic pot for 2 weeks. Then, water depletion (drought stress treatment) was applied for 1 week. Water content of the soil was decreased to less than 20%. 10 flower buds were collected for each experiment. The experiment was repeated 3-times.
2014-09-02 | E-GEOD-57174 | biostudies-arrayexpress
Project description:In S. cerevisiae, replication timing is controlled by epigenetic mechanisms restricting the accessibility of origins to limiting initiation factors. About 30% of these origins are located within repetitive DNA sequences such as the ribosomal DNA (rDNA) array, but their regulation is poorly understood. Here, we have investigated how histone deacetylases (HDACs) control the replication program in budding yeast. This analysis revealed that two HDACs, Rpd3 and Sir2, control replication timing in an opposite manner. Whereas Rpd3 delays initiation at late origins, Sir2 is required for the timely activation of early origins. Moreover, Sir2 represses initiation at rDNA origins whereas Rpd3 counteracts this effect. Remarkably, deletion of SIR2 restored normal replication in rpd3 cells by reactivating rDNA origins. Together, these data indicate that HDACs control the replication timing program in budding yeast by modulating the ability of repeated origins to compete with single-copy origins for limiting initiation factors. BrdU-IP-seq analysis of origin activity in wt, sir2 and rpd3 cells, aligned against genomic DNA (sacCer3) and rDNA sequences Please note that the wt WCE #1 and #2 samples are whole-cell extracts from wild-type cells arrested in HU that were used to calculate the log ratio of the BrdU IP #1 and #2 batches, respectively.
2014-05-14 | E-GEOD-57617 | biostudies-arrayexpress
Project description:To investigate the gene expression changes in gestational day 9 embryos exposed to hydroxyurea in utero. Agilent microarray technology was used to identify genes that responded to hydroxyurea exposure. Understanding the stress response of the embryo will help us advance education of birth defect prevention. Gestational day 9 embryos were exposed to 400 mg/kg hydroxyurea, a dose that induces a moderate number of malformations, including fetal resorptions, growth retardation, external and skeletal defects. We identified several genes involved in responding to oxidative stress, including NRF-2, PRDX1, and TXNIP. Other genes also significantly changed were involved in cell cycle arrest and apoptosis. The dysregulation in gene expression during organogenesis contributes to the developmental toxicity of hydroxyurea. Gestational day 9 mouse embryos were treated with saline or 400 mg/kg hydroxyurea by intraperitoneal injection. Dams were euthanized after 3 hours and embryos explanted. 6 indendent experiments were performed for each sample.
2015-01-15 | E-GEOD-54579 | biostudies-arrayexpress
Project description:Circulating platelets from Sickle cell disease (SCD) patients express distinct gene expression patterns that regulate function. The objective of this study is to identify a role of post-transcriptional regulation of the platelet transcriptional signaling by microRNAs. Comparison of microRNA expression in platelets from SCD patients and control subjects, from 2 cohorts-University of Pittsburgh and National Institutes of Health.
2013-06-20 | E-GEOD-41574 | biostudies-arrayexpress
Project description:MBF and SBF transcription factors regulate a large family of coordinately expressed G1/S genes required for early cell cycle functions including DNA replication and repair. SBF is inactivated upon S phase entry by Clb/CDK whereas MBF targets are repressed by the corepressor, Nrm1. Using genome-wide expression analysis, we show that genotoxic stress during S phase specifically induces MBF-regulated genes via direct phosphorylation of Nrm1 by Rad53, the effector checkpoint kinase, and prevents its binding to MBF target promoters. Interestingly, some previously defined targets of SBF, including Swe1, are activated by replication stress. Swe1 undergoes a transcription factor exchange leading to its repression by Nrm1/MBF, which renders it sensitive to derepression by the S phase checkpoint. We conclude that MBF-regulated genes are distinguished from SBF-regulated genes by their sensitivity to activation by the S phase checkpoint, thereby, providing an effective mechanism for enhancing DNA replication and repair and promoting genome stability. Modified Loop Time-series design, time points at 0, 30, 45, 60 and 75 minutes. Conditions are untreated (UT), methyl methane sulfonate (MMS-0.033%), camptothecin (CPT-50uM), and hydroxyurea (HU-0.2M)
2012-02-15 | E-GEOD-33695 | biostudies-arrayexpress
Project description:Eukaryotic DNA replication initiates from multiple sites on each chromosome called replication origins. In the budding yeast Saccharomyces cerevisiae, origins are defined at discrete sites. Regular spacing and diverse firing characteristics of origins are thought to be required for efficient completion of replication, especially in the presence of replication stress. However, a S. cerevisiae chromosome III harboring multiple origin deletions has been reported to replicate relatively normally, and yet how an origin-deficient chromosome could accomplish successful replication remains unkown. To address this issue, we deleted seven well-characterized origins from chromosome VI, and found that thsese deletions do not cause gross growth defects even in the presence of replication inhibitors. We demonstrated that the origin deletions do cause a strong decrease in the binding of the origin recognition complex. Unexpectedly, replication profiling of this chromosome showed that DNA replication initiates from non-canonical loci around deleted origins in yeast. These results suggest that replication initiation can be unexpectedly flexible in this organism. In this study, we aimed to establish an independent system to investigate how an origin-deficient chromosome is replicated. To this end, we systematically deleted seven well-characterized origins on the left arm of S. cerevisiae chromosome VI and analyzed (1) Orc2 localization during G2/M arrest and (2) BrdU incorporation during synchronous release from G1 arrest into S-phase, and compared the results to wild-type cell signals. For Orc2 ChIP-Chip experiments, Orc-bound DNA was isolated from Orc2-2Xlinker-3XFlag epitope-tagged cells arrested in G2/M using antibodies against Flag. For BrdU ChIP-Chip experiments, actively replicating DNA was isolated from cells harboring a single integrated BrdU incorporation vector released synchronously into 200mM HU using antibodies against BrdU. Immunoprecipitated and input (Orc2) or G1 (BrdU) DNA was then amplified and competitively hybridized to high-resolution strand-specific microarrays covering chromosomes III, VI, and XII.
2014-09-26 | E-GEOD-61743 | biostudies-arrayexpress