The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1999/6/1691/ $5.00
The Journal of Experimental Medicine, Volume 189, Number 11, June 7, 1999 1691-1698

Articles

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

Noboru Motoyama*, Tohru Kimura{ddagger}, Tomomi Takahashi{ddagger}, Takeshi Watanabe*, and Toru Nakano{ddagger}

From the * Department of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan; and the {ddagger} 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.

Key Words: erythrocytes • Bcl-X • apoptosis • embryonic stem cells • cell differentiation

Address correspondence to Toru Nakano, Department of Molecular Cell Biology, Research Institute for Microbial Diseases, Osaka University, Yamada-Oka 3-1, Suita, Osaka 565-0871, Japan. Phone: 81-6-6879-8361; Fax: 81-6-6879-8362; E-mail: tnakano{at}biken.osaka-u.ac.jp

N. Motoyama's present address is Department of Geriatric Research, National Institute for Longevity Sciences, 36-3 Gengo, Morioka, Obu, Aichi 474-8522, Japan.

Abbreviations used: CFU-E, colony forming unit-erythroid; EPO, erythropoietin; EryP, embryonic primitive erythrocyte(s); EryD, adult definitive erythrocyte(s); ES, embryonic stem; GPI, glucose phosphoisomerase.


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