Project description:There is increasing interest in the effects of low-dose ionizing radiation (IR) on plants as might occur during spaceflight, or as a consequence of human activities, such as nuclear power generation, that may result in the release of radioactive materials into the environment. High doses of IR have long been used for the induction of mutations in plants with the goal of generating desirable traits for agribusiness. However, less is known about the responses of plants to acute low doses of IR exposure. Here, we take a multi-omics approach to characterize the response to low dose IR in A. thaliana. We adapt the Methyltransferase Accessibility Protocol for individual templates (MAPit) technique for use in plants allowing us to assay the epigenetic response to acute low-dose IR (10 cGy and 100 cGy) 72 hr after exposure, and, in parallel, use RNA sequencing to profile the transcription response at 1, 3, 24 and 72 hr after exposure. We observe that IR exposures as low as 10 cGy elicit robust genetic responses in Arabidopsis thaliana detectable as early as 1 hr after exposure. Examination of these responses revealed dose-dependent changes in gene expression, chromatin accessibility and DNA methylation that implicate the ethylene signalling pathway and response to abiotic stress as underlying the transcriptional and epigenetic changes associated with IR. These changes are observable up to 72 hr after exposure suggesting that they are maintained well after the initial acute exposure. Our findings indicate that A. thaliana executes a coordinated, multi-modal response to low-dose IR through induction and regulation of the ethylene response pathway.
Project description:The endothelium is the barrier separating blood and tissue. Radiation-induced enhanced inflammation leading to permeability of this barrier may increase the risk of cardiovascular disease. The aim of this study was to investigate the onset of endothelial inflammatory pathways after radiation exposure. Human coronary artery endothelial cells (HCECest2) were exposed to radiation doses of 0, 0.25, 0.5, 2.0 and 10 Gy (60Co-γ). The cells were harvested 4 h, 24 h, 48 h and 1 wk post-irradiation. The proteomics analysis was performed in a label-free data-independent acquisition mode. The data were validated using bioinformatics and immunoblotting. The low- and moderate-dose-treated samples showed only small proteome changes. In contrast, an activation of DNA-damage repair, inflammation, and oxidative stress pathways was seen after high-dose treatments (2 and 10 Gy). The level of the DNA damage response protein DDB2 was enhanced early at the 10 Gy dose. The expression of proteins belonging to the inflammatory response or cGAS-STING pathway (STING, STAT1, ICAM1, ISG15) increased in a dose-dependent manner showing the strongest effects at 10 Gy after one week. This study suggests a connection between radiation-induced DNA damage and induction of inflammation and supports inhibition of cGAS-STING pathway in the prevention of radiation-induced cardiovascular disease.
Project description:Human embryonic stem cells (hESCs) present a novel platform for in vitro investigation of the early embryonic cellular response to ionizing radiation. Thus far, no study has analyzed the genome-wide transcriptional response to ionizing radiation in hESCs. In this study, we use Agilent microarrays to analyze the global gene expression changes in H9 hESCs after low (0.4 Gy), medium (2 Gy), and high (4 Gy) dose irradiation.
Project description:Low-dose radiation refers to exposure to ionizing radiation at levels that are generally considered safe and not expected to cause immediate health effects. However, the effects of low-dose radiation are still not fully understood and research in this area is ongoing. In this study, we investigated changes in gene expression in diabetic human aortic endothelial cells (T2D-HAECs) derived from type 2 diabetes patients. To this end, we used RNA-seq to profile the transcriptomes of cells exposed to varying doses of low-dose radiation (0.1Gy, 0.5Gy, and 2.0Gy) and compared them to a control group with no radiation exposure. Differentially expressed genes and enriched pathways were identified using the DESeq2 and gene set enrichment analysis (GSEA) methods, respectively. The data generated in this study are publicly available through the gene expression omnibus (GEO) database. This study provides a valuable resource for studying the effects of low-dose radiation on T2D-HAECs and can contribute to a better understanding of the potential human health risks associated with low-dose radiation exposure.
Project description:Accumulating data suggest that the biological responses to high and low doses of radiation are qualitatively different, necessitating the direct study of low dose responses. Most such studies have utilized 2-dimensional culture systems, which may not fully represent responses in 3-dimensional tissues. To gain insight into low dose responses in tissue, we have profiled global gene expression in EPI-200, a 3-dimensional tissue model that imitates the structure and function of human epidermis, at 4, 16 and 24 hours after exposure to high (2.5 Gy) and low (0.1 Gy) doses of low LET protons. The most significant gene ontology groups among genes altered in expression were consistent with effects observed at the tissue level, where the low dose was associated with gradual recovery and tissue remodeling, while the high dose resulted in loss of structural integrity and terminal differentiation. Network analysis of the significantly responding genes suggested that TP53 dominated the response to 2.5 Gy, while HNF4A, a novel transcription factor not previously associated with radiation response, was most prominent in the low dose response. Thus, these studies address the molecular basis of response to low versus high dose low LET radiation exposure.
Project description:Differentiation of hESCs to neural lineages was used as a model for early embryonic brain development in order to assess the effect of their exposure to low (17 mGy) and high (572 mGy) doses of radiation on gene expression. Exposure of hESC to the low dose did not result in changes in gene expression at any of the time points, whereas exposure to the high dose resulted in downregulation of some major neurodifferentiation markers on days 6 and 10. Gene ontology analysis showed that pathways related to nervous system development, neurogenesis, and generation of neurons were among the most affected. Conclusion: exposure to a low dose of 17 mGy was well tolerated by hESCs while exposure to 572 mGy significantly affected their genetic reprogramming into neuronal lineages.