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
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正常人 CD34+ 细胞巨核细胞和红系发育增强:SCL 强制表达的后果

DOI:
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发表时间:
1998
期刊:
影响因子:
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通讯作者:
C. Begley
C. Begley
中科院分区:
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文献类型:
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作者:
N. Elwood;H. Zogos;D. Pereira;J. Dick;C. Begley

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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,一旦建立了干细胞区室,SCL在正常造血细胞内随后的分化和定型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造血CD 34+细胞来研究这种作用。SCL逆转录病毒用于扩增从人骨髓、外周血和脐带血分离的CD 34+细胞。SCL的强制表达增加了红系细胞集落数量的两倍,集落大小和血红蛋白化率均增加。出乎意料的是,在CD 34+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。红系细胞上的SCL表达的增殖效应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不变,集落内细胞的存活也不变。这些结果表明,SCL在确定红系和巨核细胞分化的正常人造血CD 34+细胞的作用。
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.
巨噬细胞分化对白血病抑制因子/制瘤素-M/白细胞介素-6反应的差异调节:SCL转录因子强制表达的影响。
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