Cellular regulation of hemoglobin switching: evidence for inverse relationship between fetal hemoglobin synthesis and degree of maturity of human erythroid cells.
Cellular regulation of hemoglobin switching: evidence for inverse relationship between fetal hemoglobin synthesis and degree of maturity of human erythroid cells.
复制标题
血红蛋白转换的细胞调节：胎儿血红蛋白合成与人红细胞成熟度之间反比关系的证据。
DOI：
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发表时间：
1979
影响因子：
11.1
通讯作者：
G. Stamatoyannopoulos
中科院分区：
文献类型：
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作者：
T. Papayannopoulou;T. Kalmantis;G. Stamatoyannopoulos
为了研究人类红细胞的成熟水平是否影响胎儿血红蛋白程序的表达，我们研究了成人或新生儿红细胞干细胞在体外产生的红细胞克隆成熟过程中胎儿（Hb F）和成人（Hb A）血红蛋白的相对产生。在成人和新生儿细胞培养物中，与成熟克隆相比，由未成熟成红细胞组成的克隆显示出显着更高的 Hb F/Hb A 比率。促进红细胞成熟的培养条件（例如增加促红细胞生成素水平或培养时间）会降低成熟红细胞中 Hb F 的相对合成。直接免疫荧光研究表明，在成人来源的 HbF 合成克隆的成熟过程中，与 Hb A 相比，Hb F 的产生更早。研究结果表明，Hb F 的最终表达受到终末分化细胞成熟程度的影响，表明除了红系干细胞水平的调节外，在成红细胞成熟过程中还存在对 Hb F 表达的控制。 Hb F 表达与细胞成熟水平之间的反比关系表明，随着红系细胞发育的进展，整个红系干细胞分化/有红细胞成熟过程中运行的调节机制降低了 Hb F 表达的潜力。
To investigate whether the level of maturity of human erythroid cells influences the expression of the fetal hemoglobin program, we studied the relative production of fetal (Hb F) and adult (Hb A) hemoglobins during the maturation of erythroid clones produced in vitro by adult or neonatal erythroid stem cells. In both the adult and the neonatal cell cultures, clones composed of immature erythroblasts showed a significantly higher Hb F/Hb A ratio compared to the mature clones. Culture conditions enhancing erythroid cell maturity (such as an increase in the level of erythropoietin or culture time) decreased the relative synthesis of Hb F in the maturing erythroid cells. Direct immunofluorescence studies demonstrated earlier production of Hb F compared with Hb A during maturation of adult-origin HbF-synthesizing clones. The findings show that the final expression of Hb F is influenced by the degree of maturity of the terminally differentiated cells and suggest that, in addition to regulation at the level of erythroid stem cells, there is control of Hb F expression during erythroblast maturation. The inverse relationship between Hb F expression and level of cell maturity suggests that a regulatory mechanism operating throughout the process of erythroid stem cell differentiation/erythroblast maturation decreases the potential of Hb F expression as the development of the erythroid cell advances.