The early response cells to bone marrow injury

Abstract

We have previous studied the bone marrow response in submyeloablatively (6 Gy) irradiated mice. This allowed a detailed analysis of immature Lin-c-Kit+ (LK) cells only after approximately two weeks. These studies revealed significant expansion of Sca-1+ (S+) LK CD150+CD48+ cells with decreased c Kit expression level (Blood 2014 124:5112). Furthermore, they showed that not only LS+K cells responded to the injury but also Sca 1- (S-) late myeloid progenitors were activated and some of them were induced to re-expressed Sca 1 antigen. In present study, we focused on the response of LK cells occurring shortly after bone marrow damage by analyzing bone marrow 1-5 days after irradiation of mice with 2-4 Gy. The number of bone marrow cells significantly decreased after 2-4 Gy irradiation during one day. In LK cells, the LS-K/LS+K ratio decreased (below 2) due to Sca-1 induction. However, it recovered to normal level in a range of 5-7 after 3-5 days. We used CD150 and CD48 SLAM markers to distinguish between various subtypes of LSK cells, and CD34 and CD16/32 markers to characterize various types of LS-K myeloid progenitor cells. This revealed an early activation of megakaryocyte-erythroid and granulocyte macrophage myeloid progenitors. The activation was characterized by re-expression of Sca 1 in a part of these cells and by significantly decreased c-Kit expression level. During 3-5 days, c Kit recovered fully in 2 Gy- and partly in 4 Gy-irradiated mice. The transcription factor SCL/TAL1 with other co-factors is known to upregulate c-Kit gene and c-Kit expression. Therefore, we examined SCL/TAL1 mRNA level in LK cells in bone marrow of irradiated mice. Necas E, Szikszai Forgacova K, Faltusova K, et al: Lin-Sca-1+c-KitlowCD48+CD71+ Cells Are the Engine of Bone Marrow Regeneration. Blood 2014 124:5112 (abstract). Research was supported by the Grant Agency of the Czech Republic (GACR 17-01897S).