Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI.
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI.
Blood Adv. 2023 Oct 10;7(19):5727-5732. doi: 10.1182/bloodadvances.2023010088.
Our current understanding of the kinetics and dynamics of erythroid differentiation is based almost entirely on the ex vivo expansion of cultured hematopoietic progenitor cells. In this study, we used an erythroid-specific, inducible transgenic mouse line to investigate for the first time, the in vivo erythroid differentiation kinetics under steady-state conditions. We demonstrated that bipotent premegakaroycyte/erythroid (PreMegE) progenitor cells differentiate into erythroid-committed proerythroblast/basophilic erythroblasts (ProBasoE) after 6.6 days under steady-state conditions. During this process, each differentiation phase (from PreMegE to precolony forming unit-erythroid [PreCFU-E], PreCFU-E to CFU-E, and CFU-E to ProBasoE) took ∼2 days in vivo. Upon challenge with 5-flurouracil (5-FU), which leads to the induction of stress erythropoiesis, erythroid maturation time was reduced from 6.6 to 4.7 days. Furthermore, anemia induced in 5-FU-treated mice was shown to be due not only to depleted bone marrow erythroid progenitor stores but also to a block in reticulocyte exit from the bone marrow into the circulation, which differed from the mechanism induced by acute blood loss.
我们目前对红细胞分化的动力学和动态的理解几乎完全基于体外培养造血祖细胞的扩增。在这项研究中，我们使用了一种红细胞特异性、诱导型转基因小鼠品系，首次在稳态条件下研究了体内红细胞分化的动力学。我们证明，双潜能的原始巨核细胞/红细胞（PreMegE）祖细胞在稳态条件下分化为红细胞定向的成红细胞/嗜碱性成红细胞（ProBasoE）需要 6.6 天。在此过程中，每个分化阶段（从 PreMegE 到集落形成单位-红细胞前体 [PreCFU-E]，PreCFU-E 到 CFU-E，以及 CFU-E 到 ProBasoE）在体内需要约 2 天。在受到 5-氟尿嘧啶（5-FU）的挑战后，会导致应激性红细胞生成的诱导，红细胞成熟时间从 6.6 天缩短到 4.7 天。此外，5-FU 处理小鼠的贫血不仅是由于骨髓红细胞祖细胞储存减少所致，而且还由于骨髓中的网织红细胞不能进入循环而导致，这与急性失血引起的机制不同。
