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

Motoyama, Noboru; Kimura, Tohru; Takahashi, Tomomi; Watanabe, Takeshi; Nakano, Toru

doi:10.1084/jem.189.11.1691

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Article| June 07 1999

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

Noboru Motoyama,

Noboru Motoyama

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

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Tohru Kimura,

Tohru Kimura

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

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Tomomi Takahashi,

Tomomi Takahashi

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

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Takeshi Watanabe,

Takeshi Watanabe

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

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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

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Author and Article Information

Noboru Motoyama

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

Tohru Kimura

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

Tomomi Takahashi

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

Takeshi Watanabe

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

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

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: [email protected]

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

Received: September 28 1998

Revision Received: March 19 1999

Online ISSN: 1540-9538

Print ISSN: 0022-1007

1999

J Exp Med (1999) 189 (11): 1691–1698.

https://doi.org/10.1084/jem.189.11.1691

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.

1999

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