| Gao Yameng,Zhao Ke,Zhao Xiongwei,Lyu Zhichun,Li Siyu,Wu Yunqiang,Sun Huiying,Gao Huiying,Xiang Shensi,Li Changyan.Comparative study of the radiosensitivity of hematopoietic stem/progenitor cells derived from fetal liver and bone marrow[J].Chinese Journal of Radiological Medicine and Protection,2023,43(8):588-594 |
| Comparative study of the radiosensitivity of hematopoietic stem/progenitor cells derived from fetal liver and bone marrow |
| Received:April 27, 2023 |
| DOI：10.3760/cma.j.cn112271-20230427-00132 |
| KeyWords:Bone marrow-derived hematopoietic stem and progenitor cells Fetal liver-derived hematopoietic stem and progenitor cells Mitochondrial function Reconstitution capacity Radiosensitivity |
| FundProject:国家重点研发计划（2022YFA1103502） |
| Author Name | Affiliation | E-mail | | Gao Yameng | School of Basic Medicine, Anhui Medical University, Hefei 230032, China | | | Zhao Ke | Institute of Radiation Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China | | | Zhao Xiongwei | Fifth Medical Center, General Hospital of PLA, Beijing 100071, China | | | Lyu Zhichun | Institute of Radiation Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China | | | Li Siyu | School of Basic Medicine, Anhui Medical University, Hefei 230032, China | | | Wu Yunqiang | Institute of Radiation Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China | | | Sun Huiying | Institute of Radiation Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China | | | Gao Huiying | Institute of Radiation Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China | | | Xiang Shensi | Institute of Radiation Medicine, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing 100850, China | | | Li Changyan | School of Basic Medicine, Anhui Medical University, Hefei 230032, China | fmmli@163.com |
|
| Hits: 1102 |
| Download times: 288 |
| Abstract:: |
| Objective To investigate the difference in the radiation sensitivity of hematopoietic stem and progenitor cells (HSPCs) derived from fetal liver and bone marrow.Methods HSPCs from fetal liver of 14.5 d embryo or bone marrow of 8 week-old mice were isolated to receive a single dose of 5 or 10 Gy irradiation in vitro using a 60Co irradiator. Twelve hours later, the cell apoptosis, mitochondrial reactive oxygen species (ROS) level, colony formation ability and DNA damage in HSPCs were detected. Freshly isolated HSPCs were injected into lethally irradiated CD45.1+ C57BL/6J mice (4.5 Gy+5 Gy with an interval of 30 min) Chimerism rate, lineage constitution, and cell cycle were analyzed 12 weeks after transplantation.Results Compared with bone marrow HSPCs after irradiation, the percentage of apoptosis in fetal liver HSPCs was significantly higher (t=16.21, 12.27, P<0.05), the level of ROS was dramatically elevated (t=68.72, 18.89, P<0.05). At 10 Gy, fetal liver HSPCs could not form colonies at all (t=12.41, 15.67, 9.46, P<0.05). γ-H2AX immunofluorescence staining showed that the DNA damage of fetal liver HSPCs was more severe after irradiation, and the number of Foci formed was significantly higher than that of bone marrow HSPCs (t=2.27, 2.03, P<0.05), which indicated that fetal liver HSPCs were more sensitive to radiation. The chimerism rate of transplanted fetal liver HSPCs was lower than that of bone marrow cells (t=5.84, P<0.05) with a higher proportion of myeloid lineage, suggesting that fetal liver HSPCs had lower in vivo reconstitution capacity than bone marrow HSPCs and were more prone to myeloid differentiation. The cell cycle of bone marrow HSPCs from transplanted chimeric mice was examined, and the proportion of S-phase was significantly higher in the fetal liver group than that in the bone marrow group (t=2.89, P<0.05). Mitochondrial stress results showed that fetal liver HSPCs had higher basal respiratory capacity (t=39.19, P<0.05), proton leakage (t=6.64, P<0.05), ATP production (t=9.33, P<0.05), and coupling efficiency (t=7.10, P<0.05) than bone marrow c-Kit+ cells, while respiratory reserve capacity (t=5.53, P< 0.05) was lower than that of bone marrow c-Kit+ cells.Conclusions HSPCs derived from fetal liver display higher radiosensitivty compared with bone marrow HSPCs, laying the foundation for an in-depth illustration of the effects of radiation on hematopoietic stem cells at different developmental stages. |
| HTML View Full Text View/Add Comment Download reader |
| Close |
|
|
|
