Lymphoid-biased hematopoietic stem cells and myeloid-biased hematopoietic progenitor cells have radioprotection activity

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.