bcl-x Prevents Apoptotic Cell Death of Both Primitive and Definitive Erythrocytes at the End of Maturation

bcl-x is a member of the bcl-2 gene family, which regulates apoptotic cell death in various cell lineages. There is circumstantial evidence suggesting that bcl-x might play a role in the apoptosis of erythroid lineage cells, although there is no direct evidence. In this study, we used Bcl-X null mouse embryonic stem (ES) cells, and showed that Bcl-X is indispensable for the production of both embryonic primitive erythrocytes (EryP) and adult definitive erythrocytes (EryD) at the end of their maturation. In vivo, bcl-x^−/− ES cells did not contribute to circulating EryD in adult chimeric mice that were produced by blastocyst microinjection of the bcl-x^−/− ES cells. bcl-x^−/− EryP and EryD were produced by in vitro differentiation induction of ES cells on macrophage colony-stimulating factor–deficient stromal cell line OP9, and further analysis was carried out. The emergence of immature EryP and EryD from bcl-x^−/− ES cells was similar to that from bcl-x^+/+ ES cells. However, prominent cell death of bcl-x^−/− EryP and EryD occurred when the cells matured. The data show that the antiapoptotic function of bcl-x acts at the very end of erythroid maturation.