Survival or death of individual proerythroblasts results from differing erythropoietin sensitivities: a mechanism for controlled rates of erythrocyte production.
Survival or death of individual proerythroblasts results from differing erythropoietin sensitivities: a mechanism for controlled rates of erythrocyte production.
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DOI：
10.1182/blood.v82.8.2340.bloodjournal8282340
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发表时间：
1993-10
期刊：
影响因子：
20.3
通讯作者：
L. Kelley;M. Koury;M. Bondurant;S. Koury;S. Sawyer;A. Wickrema
中科院分区：
文献类型：
--
作者：
L. Kelley;M. Koury;M. Bondurant;S. Koury;S. Sawyer;A. Wickrema
小鼠红细胞祖细胞感染Friend病毒诱导贫血株（FVA细胞）后，被剥夺促红细胞生成素（EPO）后发生凋亡。当与EPO一起培养时，它们存活并完成终末分化。虽然在细胞凋亡和终末分化过程中细胞体积减小，核染色质浓缩，但在形态学和生化上观察到这两个过程的区别。在细胞凋亡中，未达到血红蛋白合成阶段的细胞发生了均匀的核凝聚和核膜丢失。在终末红细胞分化过程中，与异染色质、常染色质的核凝聚和核膜保存在血红蛋白合成的同时发生。在epo缺失的培养中，凋亡形态的细胞出现不同步，表明在任何给定时间只有一部分细胞发生凋亡。在epo缺失的培养中，凋亡细胞和断裂DNA的百分比随时间增加而增加。在广泛的生理范围内，DNA切割的抑制与EPO浓度成正比，表明基于个体细胞EPO敏感性的差异性，细胞凋亡易感性存在异质性。从缺乏EPO的培养中分离出EPO敏感性增加（EPO需求量减少）的FVA细胞亚群。这种增加的EPO敏感性不是由EPO受体数量、亲和力或结构的差异引起的，这表明差异是在信号转导途径中。这些结果表明，红细胞生成的控制既涉及EPO对细胞凋亡的预防，也涉及个体祖细胞对EPO需求的异质性。
Murine erythroid progenitors infected with the anemia-inducing strain of Friend virus (FVA cells) undergo apoptosis when deprived of erythropoietin (EPO). When cultured with EPO, they survive and complete terminal differentiation. Although cell volume is decreased and nuclear chromatin is condensed during both apoptosis and terminal differentiation, morphologic and biochemical distinctions between these two processes were observed. In apoptosis, homogeneous nuclear condensation with nuclear envelope loss occurred in cells that had not reached the stage of hemoglobin synthesis. In terminal erythroid differentiation, nuclear condensation with heterochromatin, euchromatin, and nuclear envelope preservation occurred simultaneously with hemoglobin synthesis. Cells with apoptotic morphology appeared asynchronously in EPO-deprived cultures, indicating that only a portion of the cells were undergoing apoptosis at any given time. The percentages of apoptotic cells and cleaved DNA increased with time in EPO-deprived cultures. Inhibition of DNA cleavage was directly proportional to EPO concentration over a wide physiologic range, demonstrating a heterogeneity in susceptibility to apoptosis based on variability in the EPO sensitivity of individual cells. A subpopulation of FVA cells with increased EPO sensitivity (decreased EPO requirement) was isolated from EPO-deprived cultures. This increased EPO sensitivity did not result from differences in EPO receptor number, affinity, or structure, suggesting that the differences are in the signal transduction pathway. These results indicate that control of red blood cell production involves both prevention of apoptosis by EPO and heterogeneity in the EPO requirement of individual progenitor cells.