Gene expression changes in human iPSC-derived cardiomyocytes after X-ray irradiation
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE107685 | GEO | 2018/09/03
REPOSITORIES: GEO
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2016-01-21 | E-GEOD-76484 | biostudies-arrayexpress
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Project description:Background: In the event of an improvised nuclear device detonation, the prompt radiation exposure would consist of γ rays plus a neutron component that would contribute to the total dose. As neutrons cause more complex and difficult to repair damage to cells that would result in more severe health burden to affected individuals, it is paramount to be able to estimate the contribution of neutrons to an estimated dose, to provide information for those making treatment decisions. Results: Mice exposed to either 0.25 or 1 Gy of neutron or 1 or 4 Gy x-ray radiation were sacrificed at 1 or 7 days after exposure. Whole genome microarray analysis identified 7,285 and 5,045 differentially expressed genes in the blood of mice exposed to neutron or x-ray radiation, respectively. Neutron exposure resulted in mostly downregulated genes, whereas x-rays showed both down- and up-regulated genes. A total of 34 differentially expressed genes were regulated in response to all ≥1 Gy exposures at both times. Of these, 25 genes were consistently downregulated at days 1 and 7, whereas 9 genes, including the transcription factor E2f2, showed bi-directional regulation; being downregulated at day 1, while upregulated at day 7. Gene ontology analysis revealed that genes involved in nucleic acid metabolism processes were persistently downregulated in neutron irradiated mice, whereas genes involved in lipid metabolism were upregulated in x-ray irradiated animals. Most biological processes significantly enriched at both timepoints were consistently represented by either under- or over-expressed genes. In contrast, cell cycle processes were significant among down-regulated genes at day 1, but among up-regulated genes at day 7 after exposure to either neutron or x-rays. Cell cycle genes downregulated at day 1 were mostly distinct from the cell cycle genes upregulated at day 7. However, five cell cycle genes, Fzr1, Ube2c, Ccna2, Nusap1, and Cdc25b, were both downregulated at day 1 and upregulated at day 7. Conclusions: We describe, for the first time, the gene expression profile of mouse blood cells following exposure to neutrons. We have found that neutron radiation results in both distinct and common gene expression patterns compared with x-ray radiation.
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Project description:In order to identified as candidate biomarkers for early diagonosis or as therapeutic targets in late damages of ionizing radiation, gene expression profile was analyzed in the peripheral blood of three 60Co γ-ray accidently-exposed persons. The results showed that there were 285 up-regulated and 446 down-regulated genes in irradiated samples compared with control samples. The large majority of those differentially expressed genes encode proteins that are associated with immune response, inflammation, cell structure, oxidative stress, neuro-hormone regulation, reproduction, susceptibility of psychiatric disorders, and transcriptional regulators. The expressions of IL3, KDR, CEACAM8 and OSM were validated by real-time RT-PCR method. The findings of our study should help us understanding the molecular mechanisms underlying the late effects of ionizing radiation and to develop better diagonostic and therapeutic strategies for those damages. Fresh blood samples were collected from three 60Coγ-Ray accidentally-exposed persons(3 years post irradiation) and three non-irradiated healthy donors. Leucocytes cells were isolated and total RNA was extracted. Four RNA samples, from three accidently-exposed persons and a RNA mixture extracted from a combination of three healthy donors` leucocytes (ratio 1:1:1, each 3.3×106 cells) in EL buffer, were subjected to Agilent gene expression microarray assay.
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