J. Exp. Med., Volume 189, Number 11, June 7, 1999 1691-1698

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

By Noboru Motoyama,^* Tohru Kimura, Tomomi Takahashi, Takeshi Watanabe,^* and Toru Nakano

From the ^* Department of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; and the  Department of Molecular Cell Biology, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan

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.

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