A system biology approach reveals neuronal and muscles developmental defects after chronic exposure to ionising radiation
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ABSTRACT:
ORGANISM(S): Danio rerio
PROVIDER: GSE134634 | GEO | 2020/02/04
REPOSITORIES: GEO
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Project description:Ionizing radiation (IR) affects brain development in vertebrates at early developmental stages, but its effects of IR on other developing tissues have not yet been clarified. To investigate the IR effects on the developing organs, single-cell RNA sequencing was conducted using zebrafish embryos at 24hpf.
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2015-05-18 | E-GEOD-66900 | biostudies-arrayexpress
Project description:Purpose:To help identify the role miRNAs in molecular mechanisms and pathways potentially involved in the developmental toxicity for fish exposed to Deepwater Horizon (DWH) oil, miRNA-mRNA networks in mahi-mahi (Coryphaena hippurus) embryos exposed to different DWH oils (source and artificially weathered oil) were evaluated at different critical windows of development using High Throughput Sequencing (HTS). Methods:miRNA profiles of 24, 48, 96 hpf mahi-mah larvae after slick and source oil exposure were generated by deep sequencing, in triplicate, using Illumina NextSeq v2. qRT–PCR validation was performed using SYBR Green assays. Results: Exposure of embryos to slick oil resulted in more DE miRNAs than source oil at all developmental stages 24hpf, 48hpf, and 96hpf. There was also an increase in the number of DE miRNA as development progressed, with 96hpf having the highest number of DE miRNAs. The expression of miRNAs and their target mRNA was further compared using advanced bioinformatics with subsequent target organ predictions based on their interactions. Gene ontology (GO) analysis on the target mRNAs was consistent with pathway analysis of miRNAs, predicting disruption of cardiovascular system development after oil exposure and showed that specific miRNA–mRNA interactions may contribute to these effects.
2017-12-04 | GSE102966 | GEO
Project description:Ionizing radiation (IR) has long been associated with reduced hematopoietic function and increased malignancies, although the mechanisms behind this relationship remain poorly understood. The carcinogenic effect of IR has been commonly attributed to the direct induction of DNA damage. We demonstrate that IR exposure results in long-term, somatically heritable, cell-intrinsic reductions in HSC self-renewal that is mediated by C/EBP? and reversed by Notch, both of which are associated with human leukemias. Remarkably, restoration of HSC self-renewal prevents selection for C/EBP? loss of function in previously irradiated HSC pools. We propose that environmental insults prompt HSC to initiate a program limiting their self-renewal to prevent damaged HSC from contributing to hematopoiesis. This "programmed mediocrity" is advantageous for the localized insults animals have evolved to deal with, but becomes tumor promoting when the entire HSC compartment is damaged, such as during total body irradiation, by increasing selective pressure for adaptive oncogenic mutations Examination of mRNA levels in in vitro and in vivo Hematopoietic Stem Cell that exposed to IR Ionizing radiation (IR) or control. Each group has three replicates.
2015-07-22 | E-GEOD-61602 | biostudies-arrayexpress
Project description:Peripheral blood lymphocytes from a total of 15 healthy individuals without history of cancer (NoCa) were immortalized with Epstein-Barr virus. <br><br>Cells were exposed to mock treatment (Mock), ultra-violet radiation (UV), or ionizing radiation (IR). For UV radiation treatment, cells were exposed to 10 J/m^2 and harvested for RNA 24 hours later. For IR treatment, cells were exposed to 5 Gy of IR and harvested for RNA 4 hours later. For example, NoCa1-Mock refers to cells from healthy patient 1 exposed to mock treatment. The published manuscript (NAR 32:4786, 2004) can be found at http://nar.oupjournals.org/cgi/content/abstract/32/16/4786. <br><br>Data were analyzed with Affymetrix MAS version 4.0. <br><br>Normalization -- A reference data set was generated by averaging the expression of each gene over all data sets. The data for each hybridization were compared with the reference data set in a cube root scatter plot. A linear least-squares fit to the cube root scatter plot was then used to normalize each hybridization.
2007-09-05 | E-GEOD-1977 | biostudies-arrayexpress
Project description:BACKGROUND: Ionizing radiation (IR) can be extremely harmful for human cells since an improper DNA-damage response (DDR) to IR can contribute to carcinogenesis initiation. Perturbations in DDR pathway can originate from alteration in the functionality of the microRNA-mediated gene regulation, being microRNAs (miRNAs) small noncoding RNA that act as post-transcriptional regulators of gene expression. In this study we gained insight into the role of miRNAs in the regulation of DDR to IR under microgravity, a condition of weightlessness experienced by astronauts during space missions, which could have a synergistic action on cells, increasing the risk of radiation exposure. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed miRNA expression profile of human peripheral blood lymphocytes (PBL) incubated for 4 and 24 h in normal gravity (1 g) and in modeled microgravity (MMG) during the repair time after irradiation with 0.2 and 2Gy of γ-rays. Our results show that MMG alters miRNA expression signature of irradiated PBL by decreasing the number of radio-responsive miRNAs. Moreover, let-7i*, miR-7, miR-7-1*, miR-27a, miR-144, miR-200a, miR-598, miR-650 are deregulated by the combined action of radiation and MMG. Integrated analyses of miRNA and mRNA expression profiles, carried out on PBL of the same donors, identified significant miRNA-mRNA anti-correlations of DDR pathway. Gene Ontology analysis reports that the biological category of "Response to DNA damage" is enriched when PBL are incubated in 1 g but not in MMG. Moreover, some anti-correlated genes of p53-pathway show a different expression level between 1 g and MMG. Functional validation assays using luciferase reporter constructs confirmed miRNA-mRNA interactions derived from target prediction analyses. CONCLUSIONS/SIGNIFICANCE: On the whole, by integrating the transcriptome and microRNome, we provide evidence that modeled microgravity can affects the DNA-damage response to IR in human PBL.
2012-04-09 | GSE20120 | GEO
Project description:BACKGROUND: Ionizing radiation (IR) can be extremely harmful for human cells since an improper DNA-damage response (DDR) to IR can contribute to carcinogenesis initiation. Perturbations in DDR pathway can originate from alteration in the functionality of the microRNA-mediated gene regulation, being microRNAs (miRNAs) small noncoding RNA that act as post-transcriptional regulators of gene expression. In this study we gained insight into the role of miRNAs in the regulation of DDR to IR under microgravity, a condition of weightlessness experienced by astronauts during space missions, which could have a synergistic action on cells, increasing the risk of radiation exposure. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed miRNA expression profile of human peripheral blood lymphocytes (PBL) incubated for 4 and 24 h in normal gravity (1 g) and in modeled microgravity (MMG) during the repair time after irradiation with 0.2 and 2Gy of γ-rays. Our results show that MMG alters miRNA expression signature of irradiated PBL by decreasing the number of radio-responsive miRNAs. Moreover, let-7i*, miR-7, miR-7-1*, miR-27a, miR-144, miR-200a, miR-598, miR-650 are deregulated by the combined action of radiation and MMG. Integrated analyses of miRNA and mRNA expression profiles, carried out on PBL of the same donors, identified significant miRNA-mRNA anti-correlations of DDR pathway. Gene Ontology analysis reports that the biological category of "Response to DNA damage" is enriched when PBL are incubated in 1 g but not in MMG. Moreover, some anti-correlated genes of p53-pathway show a different expression level between 1 g and MMG. Functional validation assays using luciferase reporter constructs confirmed miRNA-mRNA interactions derived from target prediction analyses. CONCLUSIONS/SIGNIFICANCE: On the whole, by integrating the transcriptome and microRNome, we provide evidence that modeled microgravity can affects the DNA-damage response to IR in human PBL.
2012-04-10 | GSE20173 | GEO
Project description:Cancer risk from medical exposure to low dose (LD) ionizing radiation (IR) is linearly extrapolated from high dose (HD) IR without sufficient mechanistic understanding and definitive evidence. The long-term health effects of radiotherapy for cancer are unclear as secondary tumours possibly arise from the ‘low-dose bath’ of normal tissue,. By the age of ~45 years, most (>90%) of the survivors of paediatric cancers develop secondary tumours from cancer therapy (including radiotherapy). Here, we show that LD and HD drive molecular and cellular responses to reactive oxygen species (ROS) production and DNA damage, respectively. We found dose-proportionality only for the phosphorylation events in the DNA damage response (DDR); signalling via PPP1R7 and global (de)phosphorylation events govern the G2/M checkpoint, whereas impaired DSB repair affected the DDR signalling duration rather than amplitudes. Contrastingly, LD specifically activated NRF2-regulated antioxidant defence, redox-sensitive ERK1/2/MAPK signalling, kinome/phosphatome, mitochondrial metabolic and glycolytic pathways, whereas HD induced replication stress signalling, p53 transcription and proliferation inhibition. Dose-proportional (10-200 mGy) chromosomal damage induction suggests non(slowly) repairable DNA breaks generation without a threshold, whereas LD-specific enhanced ROS-related responses induction implies survival of cells with residual DNA damage.
2022-07-01 | GSE130066 | GEO
Project description:Contamination of the environment after the Chernobyl and Fukushima Daiichi nuclear power plant (NPP) disasters led to the exposure of a large number of humans and wild animals to radioactive substances. However, the sub-lethal consequences induced by these absorbed radiological doses remain understudied and the long-term biological impacts largely unknown. We assessed the biological effects of chronic exposure to ionizing radiation (IR) on embryonic development by exposing zebrafish embryo from fertilization and up to 120 hours post-fertilization (hpf) at dose rates of 0.5 mGy/h, 5 mGy/h and 50 mGy/h, thereby encompassing the field of low dose rates defined at 6 mGy/h. Chronic exposure to IR altered larval behaviour in a light-dark locomotor test and affected cardiac activity at a dose rate as low as 0.5 mGy/h. The multi-omics analysis of transcriptome, proteome and transcription factor binding sites in the promoters of the deregulated genes, collectively points towards perturbations of neurogenesis, muscle development, and retinoic acid (RA) signaling after chronic exposure to IR. Whole-mount RNA in situ hybridization confirmed the impaired expression of the transcription factors her4.4 in the central nervous system and myogenin in the developing muscles of exposed embryos. At the organ level, the assessment of muscle histology by transmission electron microscopy (TEM) demonstrated myofibers disruption and altered neuromuscular junctions in exposed larvae at 5 mGy/h and 50 mGy/h. The integration of these multi-level data demonstrates that chronic exposure to low dose rates of IR has an impact on neuronal and muscle progenitor cells, that could lead to motility defects in free swimming larvae at 120 hpf. The mechanistic understanding of these effects allows us to propose a model where deregulation of RA signaling by chronic exposure to IR has pleiotropic effects on neurogenesis and muscle development.
| S-EPMC6934629 | biostudies-literature
Project description:A system biology approach reveals neuronal and muscles developmental defects after chronic exposure to ionising radiation
| PRJNA555897 | ENA