Ionizing Radiation Induced Gene Expression Alterations in Human Peripheral Blood Mononuclear Cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Lucian Beer
PROVIDER: E-GEOD-55953 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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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. Whithin 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 Human microRNA Microarrays 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-55954 | 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:In vivo antigen (Ag)-induced differentiation of B lymphocytes into plasma cells (PCs) takes place in extra-follicular foci and germinal centers of the secondary lymphoid organs (SLOs). Most of these SLO PCs are short-living and only relatively few PCs, characterized by secreting high-affinity antibodies (Ab), travel through the circulation and finally home in specialized survival niches of the bone marrow (BM) and, at a lesser extent, in the SLOs, where they become long-living Ab-secreting PCs. We have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish between human circulating Ag-induced PCs in comparison with tonsil and BM PCs distinctively regulate genes involved in cell proliferation. Gene expressions in human plasma cells isolated from tonsil (7 samples), blood (6 samples) and bone marrow (7samples) were measured. Each sample was isolated from a different donor.
2015-01-05 | E-GEOD-59697 | biostudies-arrayexpress
Project description:Background Immune tolerance and persistent mixed chimerism can be achieved reproducibly after combined organ and hematopoietic cell transplantation in mice conditioned with total lymphoid irradiation plus anti-thymocyte globulin. We studied the safety and reproducibility of this approach in a cohort of kidney transplant patients, and tried to identify immune monitoring procedures that can predict tolerance and guide complete immunosuppressive drug withdrawal. Methods Ten patients conditioned with 10 doses of total lymphoid irradiation and 5 doses of anti-thymocyte globulin were given kidney transplants and an injection of CD34+ hematopoietic progenitor cells and T cells from HLA matched donors. Blood cell monitoring included changes in chimerism, balance of T cell subsets, gene expression, and responses to donor alloantigens. Results Nine of 10 patients developed multi-lineage chimerism without graft versus host disease (GVHD), and all had excellent graft function at the last observation point. Five of these with chimerism persisting for at least 12 months were completely withdrawn from immunosuppressive drugs for 6 to 35 months. Blood cells from patients off drugs showed development of specific unresponsiveness to donor alloantigens, M-bM-^@M-^\toleranceM-bM-^@M-^] profiles on gene microarrays, early high ratios of regulatory versus conventional naM-CM-/ve T cells, and early high levels of chimerism among NK cells. Conclusions Total lymphoid irradiation, and anti-thymocyte globulin promoted the development of persistent chimerism and tolerance in a cohort of patients given kidney transplants and donor cell injections. Assays were identified that can assist in the safe withdrawal of immunosuppressive drugs. 45 Agilent Microarray samples were conducted, including 16 tolerance patients, 10 chronic rejection patients, 5 healthy normal controls, and 7 paired pre and post-transplant induced tolerance patients. The aim is to see whether induced tolerance patients show operational tolerance gene expression signature and can withdraw or minimize the immunosuppression regimens.
2012-12-15 | E-GEOD-17068 | 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: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
Project description:Transcriptional profiling of subventricular zone (SVZ) progenitors comparing control healthy mice to mice induced to develop an autoimmune demyelination (EAE model). Goal was to unveil genes involved in demyelination-induced reactivity of SVZ progenitors. Two-condition experiment, healthy vs. EAE derived SVZ progenitors. Biological replicates: 2 control replicates, 2 EAE replicates. SVZ progenitors were sorted in two cell populations: neuronal progenitors (PSA-NCAM magnetic sorting) and glial progenitors (NG2 magnetic sorting). Progenitors from healthy mice are reference samples.
2013-09-09 | E-GEOD-47486 | biostudies-arrayexpress
Project description:The immune system can recognize and respond to tumors. However there are some conditions in which the genetic instability and heterogeneity of tumor cells leads to the development of variants that can escape the immune system. T cells have infiltrated inside many tumors (Tumor Infiltrating Lymphocytes or TILs), but generally these TILs have lost their functional capacity and are unable to eliminate tumor cells. We developed a model of autochthonous melanoma in mice that recapitulates some aspects of inflammatory melanoma in humans. These include a systemic Th2/Th17-oriented chronic inflammation, recruitment of immunosuppressive myeloid cells and acquisition by TILs of an M-bM-^@M-^\exhaustedM-bM-^@M-^] phenotype characterized by expression of receptors for multiple inhibitory molecules. To address the molecular bases for the M-bM-^@M-^\exhaustedM-bM-^@M-^] TILs phenotype, we performed transcriptomic analyses on sorted CD8 or T cells from the induced melanomas. These transcriptomes were compared to those of naM-CM-/ve CD8 T cells and of CD8 T cells immunized with a virus. 10 samples, 3 replicates for controls (untreated and infected with AdP1A), 4 replicates for TILs CD8 from melanoma
2013-12-31 | E-GEOD-42824 | 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