THE ROLE OF ERYTHROPOIETIN IN REGULATION OF POPULATION SIZE AND CELL CYCLING OF EARLY AND LATE ERYTHROID PRECURSORS IN MOUSE BONE MARROW
THE ROLE OF ERYTHROPOIETIN IN REGULATION OF POPULATION SIZE AND CELL CYCLING OF EARLY AND LATE ERYTHROID PRECURSORS IN MOUSE BONE MARROW
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促红细胞生成素在调节小鼠骨髓中早期和晚期红系前体细胞数量和细胞周期中的作用
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发表时间：
1977
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通讯作者：
N. Iscove
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作者：
N. Iscove
这项研究旨在确定多潜能干细胞向造血细胞分化的阶段，在这一阶段，促红细胞生成素变得具有重要的生理意义。在高(失血后)和低(高输血后)环境条件下，监测小鼠骨髓中造血祖细胞的反应。培养2天后，通过红系集落形成检测到相对成熟的红系前体细胞(CFU-E)的数量在出血后第4天增加了3倍，在输血后减少了3倍。体外用氚胸腺嘧啶核苷(~3H-TdR)短暂作用评价CFU-E的杀伤敏感性，未处理和出血的动物CFU-E的增殖活性较高(75%杀伤)，而高血后CFU-E的增殖活性略低(60%杀伤)。更原始的红系祖细胞(BFU-E)在培养10天后通过红系集落形成检测到的反应呈现出相反的模式。在高输血后，它们略有增加，但几乎没有变化，直到出血后第四天，骨髓中的它们减少。粒细胞/巨噬细胞集落形成法检测到的祖细胞(CFU-C)也有相同的反应模式。BFU-E对~3H-TdR的敏感度正常为30%，出血后不增加，输血后不降低。然而，在再生骨髓中，BFU-E的~3H-TdR掺入灵敏度增加到63%，这种增加不受高输血的影响。这些结果被解释为：(1)促红细胞生成素的生理水平不影响多潜能造血干细胞沿着红系途径而不是粒/巨噬细胞途径分化的决定；(2)早期红系定向祖细胞本身不对这些水平的促红细胞生成素做出反应，而是受到不依赖于促红细胞生成素的机制的调节；(3)促红细胞生成素在细胞的成熟阶段开始调节，处于BFU-E和CFU-E之间的成熟阶段。
This study was designed to determine the stage in haemopoietic cell differentiation from multipotential stem cells at which erythropoietin becomes physiologically important. The responses of haemopoietic precursor cells were monitored in the bone marrow of mice under conditions of high (after bleeding) and low (after hypertransfusion) ambient erythropoietin levels. The number of relatively mature erythroid precursors (CFU‐E), detected by erythroid colony formation after 2 days of culture, increased three‐fold in marrow by the fourth day after bleeding, and decreased three‐fold after hypertransfusion. Assessed by sensitivity to killing by a brief exposure to tritiated thymidine (3H‐TdR) in vitro, the proliferative activity of CFU‐E was high (75% kill) in untreated and bled animals, and was slightly lower (60% kill) after hypertransfusion. The responses of more primitive erythroid progenitors (BFU‐E), detected by erythroid colony formation after 10 days in culture, presented a contrasting pattern. After hypertransfusion they increased slightly, while little change was noted until the fourth day after bleeding, when they decreased in the marrow. The same response pattern was observed for the progenitors (CFU‐C) detected by granulocyte/macrophage colony formation in culture. The sensitivity of BFU‐E to 3H‐TdR was normally 30%, and neither increased after bleeding nor decreased after hypertransfusion. However, in regenerating marrow the 3H‐TdR sensitivity of BFU‐E increased to 63%, and this increase was not affected by hypertransfusion. These results are interpreted as indicating (1) that physiological levels of erythropoietin do not influence the decision by multipotential haemopoietic stem cells to differentiate along the erythroid pathway as opposed to the granulocyte/macrophage pathway; (2) that early erythroid‐committed progenitors themselves do not respond to these levels of erythropoietin, but rather are subject to regulation by erythropoietin‐independent mechanisms; and (3) that physiological regulation by erythropoietin commences in cells at a stage of maturation intermediate between BFU‐E and CFU‐E.