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

doi:10.1084/jem.189.11.1691

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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, 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 regulatesapoptotic cell death in various cell lineages. There is circumstantialevidence suggesting that bcl-x might play a role in the apoptosisof 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 productionof both embryonic primitive erythrocytes (EryP) and adult definitiveerythrocytes (EryD) at the end of their maturation. In vivo,bcl-x^–/– ES cells did not contribute to circulatingEryD in adult chimeric mice that were produced by blastocystmicroinjection of the bcl-x^–/– ES cells. bcl-x^–/–EryP and EryD were produced by in vitro differentiation inductionof ES cells on macrophage colony-stimulating factor–deficientstromal 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 occurredwhen the cells matured. The data show that the antiapoptoticfunction 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 MolecularCell Biology, Research Institute for Microbial Diseases, OsakaUniversity, 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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