Enhanced megakaryocyte and erythroid development from normal human CD34(+) cells: consequence of enforced expression of SCL.
Enhanced megakaryocyte and erythroid development from normal human CD34(+) cells: consequence of enforced expression of SCL.
复制标题
正常人 CD34( ) 细胞巨核细胞和红系发育增强：SCL 强制表达的结果。
作者：
N. Elwood;H. Zogos;D. Pereira;J. Dick;C. Begley
SCL基因的产物是一种基本的螺旋-环-螺旋(BHLH)转录因子，对胚胎和成人的造血干细胞发育都是必不可少的。然而，一旦干细胞室被建立，SCL在正常造血细胞内随后的分化和承诺事件中的功能仍然不确定。本研究的目的是使用纯化的正常人CD34(+)细胞来研究这一作用。用SCL逆转录病毒转导从人骨髓、外周血和脐带血中分离的CD34(+)细胞。SCL的强制表达增加了红系集落数量的中位数的两倍，集落大小和血红素化速度都增加了。出乎意料的是，CD34(+)细胞的强制表达也显著增加了巨核细胞集落的数量，但对集落的大小没有影响。对粒细胞-巨噬细胞(GM)集落的数量和大小没有一致的影响。SCL表达增强对红系细胞的增殖作用归因于细胞周期时间的缩短；红系或GM祖细胞的自我更新能力没有变化，细胞在集落内的存活也没有变化。这些结果表明，SCL在决定正常人CD34(+)细胞向红系和巨核细胞分化的过程中发挥作用。
The product of the SCL gene is a basic helix-loop-helix (bHLH) transcription factor that is essential for the development of hematopoietic stem cells in both the embryo and the adult. However, once the stem cell compartment is established, the function of SCL in subsequent differentiation and commitment events within normal hematopoietic cells remains undefined. The aim of the current study was to investigate this role using purified normal human hematopoietic CD34(+) cells. An SCL retrovirus was used to transduce CD34(+) cells isolated from human bone marrow, peripheral blood, and umbilical cord blood. Enforced expression of SCL increased by a median of twofold the number of erythroid colonies, with an increase in both colony size and the rate of hemoglobinization. Unexpectedly, enforced expression in CD34(+) cells also significantly increased the number of megakaryocyte colonies, but with no impact on the size of colonies. There was no consistent effect on the number nor size of granulocyte-macrophage (GM) colonies. The proliferative effect of enforced SCL expression on erythroid cells was attributed to a shortened cell cycle time; the self-renewal capacity of erythroid or GM progenitors was unchanged, as was survival of cells within colonies. These results demonstrate a role for SCL in determining erythroid and megakaryocyte differentiation from normal human hematopoietic CD34(+) cells.
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影响因子：
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作者：
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作者：
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