Nielsen Julie S, Doyonnas Regis, McNagny Kelly M
The Biomedical Research Centre, University of British Columbia, Vancouver, Canada.
Cells Tissues Organs. 2002;171(1):44-63. doi: 10.1159/000057691.
E26 is an avian acute leukemia virus with a profound ability to transform multipotent hematopoietic progenitor cells both in vivo and in vitro. Progenitor cells transformed by this virus can be expanded in vitro as undifferentiated clones for up to two months and can also be induced to differentiate into cells of the erythroid, eosinophilic, thrombocytic, and myelomonocytic lineages with reproducible kinetics. Aside from the proliferative stimulus provided by the E26 oncoprotein, these cells are remarkably similar to normal hematopoietic progenitors. They therefore provide an ideal assay system for determining the influence of ectopically expressed transcription factors on both maturation and commitment to several hematopoietic lineages. Results from experiments using this system suggest that subtle shifts in the balance of lineage-restricted transcription factors can result in profound changes in phenotype and challenge the notion that lineage commitment is a uni-directional process. Analysis of the regulatory elements governing the expression of these genes has provided novel mechanistic insights into the transcriptional control of hematopoiesis. In addition to their utility in deciphering the control of lineage commitment, the ability to grow large numbers of undifferentiated and more mature hematopoietic cells has facilitated the discovery of a number of novel, lineage-restricted genes. Analysis of the proteins encoded by these genes is helping to clarify the role of a number of membrane proteins in the interaction between hematopoietic cells and their microenvironments.
E26是一种禽急性白血病病毒，在体内和体外均具有强大的转化多能造血祖细胞的能力。被这种病毒转化的祖细胞可以在体外作为未分化克隆扩增长达两个月，并且还可以被诱导以可重复的动力学分化为红系、嗜酸性粒细胞系、血小板系和骨髓单核细胞系的细胞。除了E26癌蛋白提供的增殖刺激外，这些细胞与正常造血祖细胞非常相似。因此，它们为确定异位表达的转录因子对几种造血谱系的成熟和定向分化的影响提供了理想的检测系统。使用该系统的实验结果表明，谱系限制转录因子平衡的细微变化可导致表型的深刻变化，并挑战了谱系定向分化是一个单向过程的观念。对控制这些基因表达的调控元件的分析为造血转录调控提供了新的机制见解。除了在破译谱系定向分化控制方面的效用外，大量培养未分化和更成熟造血细胞的能力促进了许多新型谱系限制基因的发现。对这些基因编码的蛋白质的分析有助于阐明许多膜蛋白在造血细胞与其微环境之间相互作用中的作用。
