[Factors controlling the differentiation and cancerization of murine erythroleukemia cells]

Cultured murine erythroleukemia (MEL) cells can be induced to differentiate into erythrocytes. During this induced differentiation, a certain type of sequentially programmed gene expression and repression appears to occur in addition to the induction of globin mRNA. This system provides a commitment model for erythrodifferentiation and decancerization. By transfection of a beta-globin/TK chimeric gene into a B8/3 cell line, we examined the regulatory factors controlling beta-globin gene expression. Our results suggested that the timing of the appearance of inducible, positive trans-acting factor (s) and activation of chromatin conformation occur during induction. We demonstrated that a novel MEL cell line, TSA 8, could be induced to be committed to CFU-E, an erythropoietin-mediated progenitor cell, with the addition of DMSO. In the commitment process, we observed an asymmetric cell division, which could explain the self-renewal and the commitment of multipotential hemopoietic stem cells. For this commitment, the receptor for erythropoietin is required, but is insufficient and the other factor (s) are induced in the earlier phase of induction. Finally, we found that erythropoietin induced two signals for proliferation and differentiation of the progenitor cells and that these two signals are not coupled.