Immediate and long-term effects of low doses of γ-irradiation on hematopoietic stem cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE66376 | GEO | 2016/02/26
SECONDARY ACCESSION(S): PRJNA277062
REPOSITORIES: GEO
Similar Datasets
Project description:Analysis of highly purified long-term hematopoietic stem cells (LT-HSCs) irradiated at 0Gy, 0.02Gy, 0.1Gy and 0.5Gy six months after transplantation. Results provide insight into the molecular mechanisms underlying multiple aspects of LT-HSCs premature ageing after low doses of γ-irradiation (0.02Gy).
2016-02-26 | GSE66375 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-02-26 | E-GEOD-66376 | biostudies-arrayexpress
Project description:Analysis of highly purified long-term hematopoietic stem cells (LT-HSCs) 2 hours after irradiation at 0Gy, 0.02Gy and 2.5Gy. Results provide insight into the molecular mechanisms underlying LT-HSCs immediate response to low doses of γ-irradiation compared to high doses.
2016-02-26 | GSE66374 | GEO
Project description:Analysis of highly purified long-term hematopoietic stem cells (LT-HSCs) irradiated at 0Gy, 0.02Gy, 0.1Gy and 0.5Gy six months after transplantation. Results provide insight into the molecular mechanisms underlying multiple aspects of LT-HSCs premature ageing after low doses of γ-irradiation (0.02Gy). Four samples were analyzed and correlated with the control group (0Gy).
2016-02-26 | E-GEOD-66375 | biostudies-arrayexpress
Project description:Analysis of highly purified long-term hematopoietic stem cells (LT-HSCs) 2 hours after irradiation at 0Gy, 0.02Gy and 2.5Gy. Results provide insight into the molecular mechanisms underlying LT-HSCs immediate response to low doses of γ-irradiation compared to high doses. Three samples were analyzed and correlated with the control group (0Gy).
2016-02-26 | E-GEOD-66374 | biostudies-arrayexpress
Project description:During deep space missions, astronauts will be exposed to low doses of charged particle irradiation. The long-term health effects of these exposures are largely unknown. We previously showed that low doses of oxygen ion (16O) irradiation induced acute damage to the hematopoietic system, including hematopoietic progenitor and stem cells in a mouse model. However, the chronic effects of low dose 16O irradiation remain undefined. In the current study, we investigated the long-term effects of low dose 16O irradiation on the mouse hematopoietic system. Male C57BL/6J mice were exposed to 0.05 Gy, 0.1 Gy, 0.25 Gy and 1.0 Gy whole body 16O (600 MeV/n) irradiation. The effects of 16O irradiation on bone marrow (BM) hematopoietic progenitor cells (HPCs) and hematopoietic stem cells (HSCs) were examined three months after the exposure. The results showed that the frequencies and numbers of BM HPCs and HSCs were significantly reduced in 0.1 Gy, 0.25 Gy and 1.0 Gy irradiated mice compared to 0.05 Gy irradiated and non-irradiated mice. Exposure of mice to low dose 16O irradiation also significantly reduced the clongenic function of BM HPCs determined by the colony-forming unit assay. The functional defect of irradiated HSCs was detected by cobblestone area-forming cell assay after exposure of mice to 0.1 Gy, 0.25 Gy and 1.0 Gy of 16O irradiation, while it was not seen at three months after 0.5 Gy and 1.0 Gy of ?-ray irradiation. These adverse effects of 16O irradiation on HSCs coincided with an increased intracellular production of reactive oxygen species (ROS). However, there were comparable levels of cellular apoptosis and DNA damage between irradiated and non-irradiated HPCs and HSCs. These data suggest that exposure to low doses of 16O irradiation induces long-term hematopoietic injury, primarily via increased ROS production in HSCs.
| S-EPMC5726652 | biostudies-literature
Project description:Our recent studies showed that total body irradiation (TBI) induces long-term bone marrow (BM) suppression in part by induction of hematopoietic stem cell (HSC) senescence through NADPH oxidase 4 (NOX4)-derived reactive oxygen species (ROS). Therefore, in this study we examined whether resveratrol (3,5,4'-trihydroxy-trans-stilbene), a potent antioxidant and a putative activator of Sirtuin 1 (Sirt1), can ameliorate TBI-induced long-term BM injury by inhibiting radiation-induced chronic oxidative stress and senescence in HSCs. Our results showed that pretreatment with resveratrol not only protected mice from TBI-induced acute BM syndrome and lethality but also ameliorated TBI-induced long-term BM injury. The latter effect is probably attributable to resveratrol-mediated reduction of chronic oxidative stress in HSCs, because resveratrol treatment significantly inhibited TBI-induced increase in ROS production in HSCs and prevented mouse BM HSCs from TBI-induced senescence, leading to a significant improvement in HSC clonogenic function and long-term engraftment after transplantation. The inhibition of TBI-induced ROS production in HSCs is probably attributable to resveratrol-mediated downregulation of NOX4 expression and upregulation of Sirt1, superoxide dismutase 2 (SOD2), and glutathione peroxidase 1 expression. Furthermore, we showed that resveratrol increased Sirt1 deacetylase activity in BM hematopoietic cells; and Ex527, a potent Sirt1 inhibitor, can attenuate resveratrol-induced SOD2 expression and the radioprotective effect of resveratrol on HSCs. These findings demonstrate that resveratrol can protect HSCs from radiation at least in part via activation of Sirt1. Therefore, resveratrol has the potential to be used as an effective therapeutic agent to ameliorate TBI-induced long-term BM injury.
| S-EPMC4711372 | biostudies-literature
Project description:Despite significant progress, the long-term health effects of exposure to high charge (Z) and energy (E) nuclei (HZEs) and the underlying mechanisms remain poorly understood. Mouse studies show that space missions can result in pulmonary pathological states. The goal of this study was to evaluate the pro-fibrotic and pro-carcinogenic effects of exposure to low doses of heavy iron ions ((56)Fe) in the mouse lung. Exposure to (56)Fe (600 MeV; 0.1, 0.2 and 0.4 Gy) resulted in minor pro-fibrotic changes, detected at the beginning of the fibrotic phase (22 weeks post exposure), which were exhibited as increased expression of chemokine Ccl3, and interleukin Il4. Epigenetic alterations were exhibited as global DNA hypermethylation, observed after exposure to 0.4 Gy. Cadm1, Cdh13, Cdkn1c, Mthfr and Sfrp1 were significantly hypermethylated after exposure to 0.1 Gy, while exposure to higher doses resulted in hypermethylation of Cdkn1c only. However, expression of these genes was not affected by any dose. Congruently with the observed patterns of global DNA methylation, DNA repetitive elements were hypermethylated after exposure to 0.4 Gy, with minor changes observed after exposure to lower doses. Importantly, hypermethylation of repetitive elements coincided with their transcriptional repression. The findings of this study will aid in understanding molecular determinants of pathological states associated with exposure to (56)Fe, as well as serve as robust biomarkers for the delayed effects of irradiation. Further studies are clearly needed to investigate the persistence and outcomes of molecular alterations long term after exposure.
| S-EPMC4100002 | biostudies-literature
Project description:The biological effects of low-dose or low-dose-rate ionizing radiation on normal tissues has attracted attention. Based on previous research, we observed the morphology of liver tissues of C57BL/6J mice that received <50, 50-500, and 500-1000 ?Gy/h of 137Cs radiation for 180 d. We found that the pathological changes in liver tissues were more obvious as the irradiation dose rates increased. Additionally, differential protein expression in liver tissues was analyzed using a proteomics approach. Compared with the matched group in the 2D gel analysis of the irradiated groups, 69 proteins had ? 1.5-fold changes in expression. Twenty-three proteins were selected based on ?2.5-fold change in expression, and 22 of them were meaningful for bioinformatics and protein fingerprinting analysis. These molecules were relevant to cytoskeleton processes, cell metabolism, biological defense, mitochondrial damage, detoxification and tumorigenesis. The results from real-time PCR and western blot (WB) analyses showed that calreticulin (CRT) was up-regulated in the irradiated groups, which indicates that CRT may be relevant to stress reactions when mouse livers are exposed to low-dose irradiation and that low-dose-rate ionizing radiation may pose a cancer risk. The CRT protein can be a potential candidate for low-dose or low-dose-rate ionizing radiation early-warning biomarkers. However, the underlying mechanism requires further investigation.
| S-EPMC5607120 | biostudies-literature
Project description:The production of blood cells depends on a rare hematopoietic stem-cell (HSC) population, but the molecular mechanisms underlying HSC biology remain incompletely understood. Here, we identify a subset of microRNAs (miRNAs) that is enriched in HSCs compared with other bone-marrow cells. An in vivo gain-of-function screen found that three of these miRNAs conferred a competitive advantage to engrafting hematopoietic cells, whereas other HSC miRNAs attenuated production of blood cells. Overexpression of the most advantageous miRNA, miR-125b, caused a dose-dependent myeloproliferative disorder that progressed to a lethal myeloid leukemia in mice and also enhanced hematopoietic engraftment in human immune system mice. Our study identifies an evolutionarily conserved subset of miRNAs that is expressed in HSCs and functions to modulate hematopoietic output.
| S-EPMC2922591 | biostudies-literature