Gene expression changes in human iPSC-derived cardiomyocytes after X-ray irradiation
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE107685 | GEO | 2018/09/03
REPOSITORIES: GEO
Similar Datasets
Project description:Proton (PT) therapy represents an alternative to conventional X-ray therapy, and its clinical application for cancer treatment is on the rise due to associated dose deposit advantages. However, our knowledge of biological responses to PT, in comparison to X-ray, remains in its infancy. Identification of PT specific molecular signals is an important opportunity for the discovery of biomarkers and synergistic drugs. We have profiled the transcriptome regulation of lymphoma cells exposed to clinical sources of PT and X-ray radiation, respectively. Subsequent analysis demonstrated both common and radiation-specific deregulation of gene expression. Gene set enrichment discovered pathways unique to PT \ that contribute to the unfolded protein response (UPR) and mitochondrial transport.
2022-01-03 | GSE143550 | GEO
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.
2017-02-01 | GSE85323 | GEO
Project description:Glioblastoma (GBM) is a devastating malignant brain tumor with a poor prognosis. GBM is associated with radio-resistance. Post-translational modifications (PTMs) such as protein phosphorylation can play an important role in the cellular response to radiation. To better understand the early cellular activities after radiation in GBM, we carried out a phospho-proteomic study on the U251 cell line, 3h after X-ray irradiation (6Gy) and on non-irradiated cells.
2024-11-07 | PXD057642 |
Project description:This dataset is composed by the transcriptomic, proteomic and phosphoproteomic profile of primary human fibroblasts exposed to two different doses of radiation: an acute X-ray radiation dose, and an accumulative X-ray radiation dose. These data were employed to apply and evaluate different computational approaches to model and infer cellular signaling processes through the combination of prior knowledge and omic data. We employed RNA-Seq and Mass Spectrometry (MS) to generate the transcriptomic and proteomic data from the RNA and protein samples, respectively.
2023-01-01 | E-MTAB-10456 | biostudies-arrayexpress
Project description:Background: In the event of an improvised nuclear device or radiological dirty bomb detonation large numbers of people will be exposed to radiation that would require a timely and accurate biodosimetry to identify the highly exposed individuals who would require medical treatment from those who have received low or no radiation (the “worried well”). Gene expression signatures in response to radiation have been derived from mice and human peripheral blood and the impact of a number of variables, such as dose, time, genotype, and gender, on gene expression has been analyzed. However, the impact of aging on radiation gene profiling has not been taken into consideration. Results: Global gene expression was measured in the blood of young (2 mo) and old (21 mo) male C57BL/6J mice 1 day after they were exposed to 4 Gy x-rays or they were sham irradiated (control) using the Agilent Mouse Whole Genome microarrays. Animals exposed to radiation suppressed expression of DNA repair genes with fold-changes being very similar to the two age groups. A notable exception was Mismatch Repair (MMR) that was significantly enriched among the downregulated genes in irradiated old mice (p = 2.34E-09) compared with irradiated young mice (p = 1.62E-04). Furthermore, cardiac hypertrophy signaling (p < 0.002) and the role of NFAT in cardiac hypertrophy (p = 0.01) were predicted to be enriched among the upregulated differentially expressed genes in irradiated old mice, but not irradiated young mice. In contrast, young mice respond to x-ray exposure by significantly upregulating genes involved in phagosome formation (p = 3.09E-07), phagosome maturation (p = 0.001), and Fcγ receptor-mediated phagocytosis (p = 0.03), all crucial processes that eliminates apoptotic cells and preserve tissue homeostasis. Conclusions: We show that age is a variable that has the potential to fundamentally alter the transcriptomic profile of irradiated mouse blood. A number of biological processes, including phagocytosis, are differentially represented in young and old mice exposed to x-ray radiation. Our results highlight the significance of age as a variable that can have profound biological effects that will affect medical management and treatment decisions in case of a radiological emergency.
2021-05-19 | GSE132559 | GEO
Project description:Nanostring gene expression analysis using tumors from mice treated with GLA, X-ray radiation or the combination of GLA and radiation showed that the combination of GLA and radiation has synergistic effect in modulating the tumor micronenvironment.
2021-12-22 | GSE178553 | GEO
Project description:In recent years there is a growing epidemiological indication of excess risk of cardiovascular disease at low doses of ionizing radiation without a clear-cut threshold. It is proposed that damage to the vascular endothelium is critical in radiation-related cardiovascular diseases. In order to identify and better understand the underlying molecular mechanisms of high LET (Fe ions) and low LET (X-ray) radiation on endothelial cells, we performed a microarray analysis on immortalized human coronary artery endothelial cells irradiated with 2.00 Gy and compared them with sham-irradiated samples. RNA was extracted at different time points after irradiation (1 day, 7 days).
2017-10-02 | E-MTAB-5754 | biostudies-arrayexpress
Project description:Here, male and female B6C3F1 mice were given single or fractionated whole-body exposure(s) to a monoenergetic carbon ion radiotherapy beam at the Heavy Ion Medical Accelerator in Chiba, Japan, matching the radiation quality delivered to the normal tissue ahead of the tumour volume. These mice were then monitored for the remainder of their lifespan and a large number of T cell lymphomas were analysed, alongside those arising in mice exposed to equivalent doses of standard Cs137 gamma ray-irradiation. Using genome-wide DNA copy number analysis to identify genomic loci involved in radiation-induced lymphomagenesis and subsequent detailed analysis of Notch1, Ikaros, Pten, Trp53 and Bcl11b genes we compared the genetic profile of the carbon ion- and gamma ray-induced tumours. The canonical set of genes previously associated with radiation-induced T cell lymphoma was identified in both radiation groups. While the pattern of disruption of the various pathways was somewhat different between the radiation types, most notably Pten mutation frequency and loss of heterozygosity flanking Bcl11b, the most striking finding was the observation of large interstitial deletions at various sites across the genome in carbon ion-induced tumours, which were only seen infrequently in the gamma ray-induced tumours analysed. 32 unique tumours (12 gamma ray-induced, 20 carbon ion-induced) each with sex-matched reference DNA
2015-03-03 | E-GEOD-61315 | biostudies-arrayexpress
Project description:ABSTRACT Background: Viral myocarditis is a life-threatening illness that may lead to heart failure or cardiac arrhythmias. This study examined whether human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) could be used to model the pathogenic processes of coxsackievirus-induced viral myocarditis and to screen antiviral therapeutics for efficacy. Methods and Results: Human iPSC-CMs were infected with a luciferase-expressing mutant of the coxsackievirus B3 strain (CVB3-Luc). Brightfield microscopy, immunofluorescence, and calcium imaging were used to characterize virally infected hiPSC-CMs. Viral proliferation on hiPSC-CMs was subsequently quantified using bioluminescence imaging. For drug screening, select antiviral compounds including interferon beta 1 (IFNβ1), ribavirin, pyrrolidine dithiocarbamate (PDTC), and fluoxetine were tested for their capacity to abrogate CVB3-Luc proliferation in hiPSC-CMs in vitro. The ability of some of these compounds to reduce CVB3-Luc proliferation in hiPSC-CMs was consistent with the reported drug effects in previous studies. Finally, mechanistic analyses via gene expression profiling of hiPSC-CMs infected with CVB3-Luc revealed an activation of viral RNA and protein clearance pathways within these hiPSC-CMs after IFNβ1 treatment. Conclusions: This study demonstrates that hiPSC-CMs express the coxsackievirus and adenovirus receptor, are susceptible to coxsackievirus infection, and can be used to confirm antiviral drug efficacy. Our results suggest that the hiPSC-CM/CVB3-Luc assay is a sensitive platform that could be used to screen novel antiviral therapeutics for their effectiveness in a high-throughput fashion. For this experiment, human induced pluripotent stem cell derived cardiomyocytes were infected with coxsackievirus at multiplicity of infection (MOI) of 5 for 8 hours. Cells were treated with and without interferon beta 1 in order to determine if treatment activates antiviral response genes and/or viral clearance pathways. 4 total samples (2 for each condition) were analyzed
2014-05-19 | E-GEOD-57781 | biostudies-arrayexpress
Project description:Studies of radiation exposed populations have shown that children are at greater overall risk of radiation-induced cancer, although there is considerable debate relating to heterogeneity of the effect in different tissues. Given public concern around increasing radiation doses received by children from advanced diagnostic imaging, and the use of radiotherapy to treat childhood cancers, understanding the relationship between age-at-exposure and radiation-induced cancer risk is a priority of radiation protection research. Although tobacco smoking accounts for up to 90% of lung cancers in some countries, epidemiological studies and animal experiments show that exposure to ionizing radiation is also a risk factor for developing cancers of the lung. Female Wistar rats are susceptible to lung cancer upon thoracic X-ray irradiation, developing adenocarcinomas (AC) and squamous cell carcinomas (SCC) similar to those seen in humans, and have been used previously to evaluate the interaction of radiation and a chemical carcinogen in neonatal, juvenile and young adult rats. In the present study, the induction of lung tumors was analyzed in female Wistar rats exposed to increasing doses of thoracic X-rays as neonates, juveniles or adults, to allow the effect of age-at-exposure to be observed in the absence of interaction with smoking. Histology was used to compare tumor subtypes between groups, and genomic DNA copy number alterations in a number of tumors arising after exposure to radiation at different ages were examined.
2017-03-03 | GSE78869 | GEO