Zhang Shanshan, O'Neill Aled, Xie Miner, Wu Peng, Wang Xiaofang, Bai Haitao, Dong Fang, Wang Jinhong, Zhang Qingyun, Suda Toshio, Ema Hideo
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Hematological Disorders, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.
Department of Cell Differentiation, Sakaguchi Laboratories of Developmental Biology, Keio University School of Medicine, Tokyo, Japan.
Blood Sci. 2021 Aug 19;3(4):113-121. doi: 10.1097/BS9.0000000000000089. eCollection 2021 Oct.
Radioprotection was previously considered as a function of hematopoietic stem cells (HSCs). However, recent studies have reported its activity in hematopoietic progenitor cells (HPCs). To address this issue, we compared the radioprotection activity in 2 subsets of HSCs (nHSC1 and 2 populations) and 4 subsets of HPCs (nHPC1-4 populations) of the mouse bone marrow, in relation to their in vitro and in vivo colony-forming activity. Significant radioprotection activity was detected in the nHSC2 population enriched in lymphoid-biased HSCs. Moderate radioprotection activity was detected in nHPC1 and 2 populations enriched in myeloid-biased HPCs. Low radioprotection activity was detected in the nHSC1 enriched in myeloid-biased HSCs. No radioprotection activity was detected in the nHPC3 and 4 populations that included MPP4 (LMPP). Single-cell colony assay combined with flow cytometry analysis showed that the nHSC1, nHSC2, nHPC1, and nHPC2 populations had the neutrophils/macrophages/erythroblasts/megakaryocytes (nmEMk) differentiation potential whereas the nHPC3 and 4 populations had only the nm differentiation potential. Varying day 12 spleen colony-forming units (day 12 CFU-S) were detected in the nHSC1, nHSC2, and nHPC1-3 populations, but very few in the nHPC4 population. These data suggested that nmEMk differentiation potential and day 12 CFU-S activity are partially associated with radioprotection activity. Reconstitution analysis showed that sufficient myeloid reconstitution around 12 to 14 days after transplantation was critical for radioprotection. This study implied that radioprotection is specific to neither HSC nor HPC populations, and that lymphoid-biased HSCs and myeloid-biased HPCs as populations play a major role in radioprotection.
辐射防护以前被认为是造血干细胞（HSC）的一项功能。然而，最近的研究报道了其在造血祖细胞（HPC）中的活性。为解决这个问题，我们比较了小鼠骨髓中HSC的2个子集（nHSC1和2个群体）和HPC的4个子集（nHPC1 - 4个群体）的辐射防护活性，并将其与它们的体外和体内集落形成活性相关联。在富含淋巴偏向性HSC的nHSC2群体中检测到显著的辐射防护活性。在富含髓系偏向性HPC的nHPC1和2群体中检测到中等程度的辐射防护活性。在富含髓系偏向性HSC的nHSC1中检测到低辐射防护活性。在包含MPP4（LMPP）的nHPC3和4群体中未检测到辐射防护活性。单细胞集落测定结合流式细胞术分析表明，nHSC1、nHSC2、nHPC1和nHPC2群体具有中性粒细胞/巨噬细胞/红细胞/巨核细胞（nmEMk）分化潜能，而nHPC3和4群体仅具有nm分化潜能。在nHSC1、nHSC2和nHPC1 - 3群体中检测到不同数量的第12天脾集落形成单位（第12天CFU - S），但在nHPC4群体中很少。这些数据表明，nmEMk分化潜能和第12天CFU - S活性与辐射防护活性部分相关。重建分析表明，移植后约12至14天足够的髓系重建对辐射防护至关重要。这项研究表明，辐射防护并非特定于HSC或HPC群体，并且作为群体的淋巴偏向性HSC和髓系偏向性HPC在辐射防护中起主要作用。
