Elwood N J, Zogos H, Pereira D S, Dick J E, Begley C G
Rotary Bone Marrow Research Laboratories, Victoria, Australia.
Blood. 1998 May 15;91(10):3756-65.
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.
SCL基因的产物是一种碱性螺旋-环-螺旋（bHLH）转录因子，对胚胎和成人造血干细胞的发育至关重要。然而，一旦干细胞区室建立，SCL在正常造血细胞随后的分化和定向事件中的功能仍不明确。本研究的目的是使用纯化的正常人造血CD34(+)细胞来研究这一作用。一种SCL逆转录病毒被用于转导从人骨髓、外周血和脐带血中分离出的CD34(+)细胞。SCL的强制表达使红系集落数量中位数增加了两倍，集落大小和血红蛋白化速率均增加。出乎意料的是，CD34(+)细胞中的强制表达也显著增加了巨核细胞集落的数量，但对集落大小没有影响。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强制表达对红系细胞的增殖作用归因于细胞周期时间缩短；红系或GM祖细胞的自我更新能力未改变，集落内细胞的存活率也未改变。这些结果证明了SCL在决定正常人造血CD34(+)细胞向红系和巨核系分化中的作用。
