Ionizing Radiation Induced micro RNA Expression Alterations in Human Peripheral Blood Mononuclear Cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Lucian Beer
PROVIDER: E-GEOD-55954 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Ionizing Radition is known to cause cell damage. Human peripheral blood mononuclear cells have long been used to study radiation induced gene expression profiling. Within this study we evaluated gene and microRNA expression alterations of human PBMC irradiated with 60 Gy g-ray. Cells were cultured for 2, 4 and 20h after irradiation before RNA was isolated and Agilent whole human GenomeOligo Microarray was performed. Radiation induced gene expression in human peripheral blood mononuclear cells were measured at 2, 4 and 20 hours after exposure to doses of 60 Gy g-rays. Non radiated cell of each donor and time point were used as contol cells. Four independent experiments were performed at each time (2, 4, or 20 hours and 0 h - only 1 sample per donor) using 4 different donors.
2014-09-26 | E-GEOD-55953 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-09-26 | E-GEOD-55955 | biostudies-arrayexpress
Project description:Oncogenic NRAS mutations are frequently identified in human myeloid leukemias. In mice, expression of endogenous oncogenic Nras (NrasG12D/+) in hematopoietic cells leads to expansion of myeloid progenitors, increased long-term reconstitution of bone marrow cells, and a chronic myeloproliferative neoplasm (MPN). However, acute expression of NrasG12D/+ in a pure C57BL/6 background does not induce hyperactivated GM-CSF signaling or increased proliferation in myeloid progenitors. It is thus unclear how NrasG12D/+ signaling promotes leukemogenesis. Here we show that hematopoietic stem cells (HSCs) expressing NrasG12D/+ serve as MPN initiating cells. They undergo moderate hyperproliferation with increased self-renewal. The aberrant NrasG12D/+ HSC function is associated with hyperactivation of ERK1/2 in HSCs. Conversely, downregulation of MEK/ERK by pharmacological and genetic approaches attenuates the cycling of NrasG12D/+ HSCs and prevents the expansion of NrasG12D/+ HSCs and myeloid progenitors. Our data delineate critical mechanisms of oncogenic Nras signaling in HSC function and leukemogenesis. three NrasG12D/G12D HSCs samples, three NrasG12D/+ HSCs samples, two Nras+/+ HSCs control samples.
2013-05-29 | E-GEOD-46948 | biostudies-arrayexpress
Project description:We studied the radiation effect on cell culture model of oral mucositis. The musositis model (tissues) used is an organotypic model which consisted of 3-dimensional (3-D) cell cultures of primary human oral keratinocytes. The tissues were purchased from MatTek corporation (Ashland, MA) and were grown on top of microporous membrane and supplemented with MatTek serum free media. These tissues were irradiated with 12 Gy. Six hours after the irradiation the tissues were cut in half. Half of the tissue was used to extract total RNA (RNeasy Plus Mini kit, Qiagen, Germantown, MD) and the other half was used to evaluate the histology and the apoptosis. We had the following groups: Non-Irradiated Tissue, Irradiated Tissue with 12 Gy; Irradiated Tissue with 12 Gy pretreated with N-acetylcysteine (ACS); Irradiated Tissue with 12 Gy pretreated with the Traditional Chinese Medicine (TCM) Qingre-Liyan decoction; and Irradiated Tissue with 12 Gy pretreated with 50:50 w/w ACS:TCM (AT) Group 1: Human Prirmary 3-D Cultures of Human Keratinocytes were irradiated with 12 Gy; Group 2: Human Prirmary 3-D Cultures of Human Keratinocytes were pretereated with N-acetylcysteine (ACS) and then irradiated with 12 Gy; Human Prirmary 3-D Cultures of Human Keratinocytes were pretreated with the Traditional Chinese Medicine (TCM), Qingre-Liyan Decostion and then irradiated with 12 Gy; Human Prirmary 3-D Cultures of Human Keratinocytes were pretreated with a 50:50 w/w mixture of ACS:TCM (AT) and then irradiated with 12 Gy. Each sample was done in triplicate.
2014-10-16 | E-GEOD-62397 | biostudies-arrayexpress
Project description:We used whole genome transcriptome as gene discovery to further understand the differential behaviour of the first (embryonic) and second waves of thymic settling progenitors in the murine embryo. Mouse embryos at days 13 and 18 of gestation were isolated and the thymic lobes were dissected. Single cell suspension was prepared and treated with biotinilated antibodies to CD3, CD4, CD8, TER119, Gr1, CD25, CD19, NK1.1 and CD11c. Cell suspensions were then incubated with streptavidin Miltenyi Macs beads. Lineage negative thymocytes were recovered in Macs columns. Cell suspensions were then incubated with antibodies against CD135, CD117, CD44, CD24 and Streptavidin bound to PECy7. Lin-, CD117+, CD44+, CD24low, CD135+ cells were then isolated by cell sorting. 3 biological replicates of each sample were isolated with 104-3x104 cells
2013-09-17 | E-GEOD-50910 | biostudies-arrayexpress
Project description:Ataxia telangiectasia (AT) is an autosomal recessive disorder characterized by neuronal degeneration, telangiectasias, acute cancer predisposition, and hypersensitivity to ionizing radiation (IR). The gene defective in AT, ATM (for AT-mutated), encodes a protein, pATM that has been found to have IR-inducible kinase activity. Cells from individuals with AT exhibit severely attenuated cell cycle checkpoints in response to gamma radiation exposure. pATM has been hypothesized to act as part of a complex that senses DNA damage, in particular, DNA double strand breaks. We are studying the pATM-dependent gene expression responses to a dose of 1.5 Gy radiation in lymphoblastoid cell lines from multiple individuals with either wild type or mutated ATM. The gene expression analyses were performed on Agilent Human 1A Oligo chips containing approximately 16,000 60mer probes. We identified a set of genes whose gene expression changes are ATM-dependent following exposure to 1.5 Gy IR. This set of genes was tested by real time quantitative PCR analysis. The study consists of one dose group - 1.5 Gray gamma radiation. Samples were collected 6 hr following irradiation (treated) or mock irradiation (controls) for each culture. Each culture has a treated sample and a control sample. There are cultures from 6 wild-type ATM individuals and cultures from 6 individuals that are ATM-deficient, for a total of 12 cultures. Hybridizations compared RNA extracted from each individual culture's treated sample against its corresponding control sample, and were performed as dye-flip duplicates (1 replicate in each direction). Hybridizations were performed on the Human 1A Oligo Chips using low input, direct labeling at Paradigm Genetics Laboratory. Microarray scanning was performed with the Agilent G2565AA Scanner. Paradigm Standard Operating Procedures were followed for quality analysis, sample labeling, microarray hybridization and washing, scanning, image analysis and initial data analysis.
2013-12-02 | E-GEOD-19287 | biostudies-arrayexpress
Project description:To compare expression profiles in the cardiomyocytes with wild type top2b and those with top2b deletion after in vivo treatment of mice with doxorubicin or drug vehicle Doxorubicin is widely used in modern cancer treatments, despite the advent of targeted therapy. However, a dose-dependent cardiotoxicity often limits its clinical use. The prevailing theory hypothesizes that doxorubicin-induced cardiotoxicity is the result of reactive oxygen species (ROS) generation due to redox-cycling of doxorubicin. Here we showed that cardiomyocyte-specific deletion of Topoisomerase II beta (Top2b) markedly reduced DNA double-strand breaks, apoptosis, and functional damages in doxorubicin-treated hearts. To investigate transcriptomic changes after doxorubicin treatment in wild type mouse and mouse with cardiac specific deletion of Top2b, we examined the expression profiles in 4 groups of mice (3/group), ie. wildtype mice with or without doxorubicin treatment and mice with Top2b deletion in the cardiomyocytes with or without doxorubicin treatment. Mice were treated with doxorubicin (25mg/kg, i.p.) or PBS (drug vehicle) for 16 hr or 72 hr. The heart was removed and cardiomyocytes were isolated by using a Langendorff apparatus. After purification, total RNA was extracted from the cardiomyocytes, purified, and used for gene expression analysis. Compared with that in control cardiomyocytes or cardiomyocytes with Top2b deletion, doxorubicin caused a significant expression change in the genome of cardiomyocytes from the wildtype mice. Among the changes, multiple genes encoding mitochondrial structural protein and components of the respiratory chain complexes were down-regulated 72 hr after treatment while multiple genes in the p53 pathway were up-regulated 16 hr after treatment in the wildtype cardiomyocytes. Expression changes were examined in 2 groups of mice (wild type and conditional knockout of top2b in the cardiomyocytes) treated with doxorubicin or PBS for 16 or 72 hours
2012-10-28 | E-GEOD-40289 | biostudies-arrayexpress
Project description:In order to identify some lncRNA potentially involved in Rett syndrome we performed a mouse lncRNA expression microarray on whole brain samples coming from wild-type and MeCP2 Knock-out littermates. We found 2 lncRNAs directly bound by MeCP2 and upregulated in KO samples. We then focused on AK081227 because it overlaps with Gabrr2. The expression of this GABA receptor and the overlapping AK081227 are inversely correlated in thalamus, suggesting the long non-coding is regulating his own host. Whole brain total RNA was extracted from two Wild type mice (P60) and two MeCP2 KO littermates (P60)
2013-10-03 | E-GEOD-43689 | biostudies-arrayexpress
Project description:NQO1 silencing by a specific shRNA against NQO1 increased migration and hormone-independent survival in hormone-dependent human prostate cancer cells LNCaP. Genome wide array revealed that NQO1 blockade significantly upregulated pro-inflammatory mediators (e.g., IL-32, CCL2, IL-8, IL-17C, IL-10RA, CXCR2, CXCR7, NOS3) associated with prostate tumorigenesis. Two-condition experiment, control vs. NQO1 knockdown LNCaP cells. Biological replicates: 3 control replicates, 3 NQO1 knockdown replicates.
2014-08-26 | E-GEOD-58336 | biostudies-arrayexpress
Project description:Background: The radiation bystander response is an important component of the overall response of cells to radiation and critical to understanding health risks of radiation exposure to humans. The mechanism of radiation response includes inter-cellular signaling and intra-cellular communication by which the bystander signal is propagated. Methods: We measured the bystander response to 1Gy a-particle radiation in Mrad9-/- mouse stem cells and H1299shRAD9 cells, using chromosomal aberration and micronucleus formation as DNA damage endpoints. In the H1299 model we used whole genome microarray analyses to profile the transcriptome of irradiated and bystander cells. Results: We investigated the role of RAD9 in the bystander response and showed that depletion or mutation of RAD9 had an effect of increasing chromosomal structural damage as well as micronucleus formation in bystander cells. The enhancement of the damage effect correlated strongly with a transcriptomic response in critical pathways. RAD9 depletion affected many pathways in the cell, including the UV-MAPK pathway, involving p38MAPK members, STAT1 and PARP1 at the mRNA levels. There was an overall reduction of RNA biogenesis of gene members of this pathway suggesting that perhaps these signaling pathways do not function optimally after RAD9 depletion. Using network analysis we found there may be differential activation of transcriptional regulators between the irradiated and bystander cells involving the SP1 and NUPR1 transcription factors. Network analysis also suggested that HIF1a (Hypoxia induced factor 1a) activation could be a negative predictor of the bystander effect and perhaps that local hypoxic stress observed by cells that are directly exposed to radiation may predict whether or not they will elicit a bystander response. Gene expression in H1299 cells was measured at 4 hours after exposure to 1 Gy a-particles. There were two groups based on RAD9 status, RAD9 normal and RAD9 depleted by siRNA. In each of these groups, sham irradiated, direct irradiated cells for positive bystanders, positive bystanders, direct irradiated cells for negative bystanders and negative bystanders; were identified based on micronucleus responses. Five biological replicates were analyzed for each experimental group.
2014-10-07 | E-GEOD-55869 | biostudies-arrayexpress