Regulation of gene expression in erythropoiesis

小鼠红白血病（MEL）细胞的体外诱导分化是分析细胞定向分化过程中分子事件的良好系统。我们发现，MEL细胞之一的TSA 8细胞经DMSO处理后，对促红细胞生成素（epo）产生定向反应，形成分化的红系祖细胞集落。在诱导过程中，epo表面受体的数量和亲和力没有变化，因此，细胞内诱导的细胞因子是获得epo反应性所必需的。两个独立的因子的参与被证明是必要的承诺;一个是环己酰亚胺敏感的因子，它出现在添加DMSO后，另一个是Na^+/H^+转运蛋白，它对苯胺衍生物敏感，并出现在后期的承诺过程。为了检测细胞癌基因在定向过程中的作用，将与金属硫蛋白启动子连锁的c-myc基因导入MEL细胞，观察了c-myc基因对MEL细胞定向过程的影响，但分析了过量产生的c-myc产物。结果表明，c-myc基因的表达水平决定了Mel细胞定向分化的可能性，c-myc基因可能在Mel细胞定向分化过程中起着与组织特异性基因表达时间相联系的作用。

The induced differentiation of murine erythroleukemia(MEL) cells in vitro is a good system to analyze the molecular events underlining the commitment process of cell differentiation. We found that TSA8 cells, one of MEL cells were committed to respond to erythropoietin(epo) and to form the differentiated colonies of erythroid progenitor cells, when the cells were treated with DMSO. In the induced process, the surface receptors for epo did not change in their number and in their affinities, thus, the intracellular factors induced in the cells are required for the acquisition of responsiveness to epo. The involvement of two independent factors are shown to be required for the commitment; one is the cycloheximide-sensitive factor which appears just after the addition of DMSO, the other is the Na^+/H^+ transporter which is sensitive to anyloride derivatives and appears in the later process of commitment. Thus, the commitment may be controlled by the sequential appearance of two factors, The signal transduction induced by epo was analyzed and the results indicated that a cAMP pathway is mainly involved in the epo action.To examine the involvement of cellular onco genes in the commitment process, the methallothionein promoter-linked c-myc gene was introduced into MEL cells and the effect of the regulated, but over-produced c-myc products was analyzed. The results indicated that the level of c-myc determines the probability of commitment of differentiation of Mel cells, Furthermore, c-myc may function to link the commitment process and the timing of expression of tissue-specific genes.