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.