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The Journal of Immunology, 2006, 177: 7733-7739.
Copyright © 2006 by The American Association of Immunologists, Inc.

Expression of Integrin beta3 Is Correlated to the Properties of Quiescent Hemopoietic Stem Cells Possessing the Side Population Phenotype1

Terumasa Umemoto*, Masayuki Yamato*, Yoshiko Shiratsuchi{dagger}, Masao Terasawa{dagger}, Joseph Yang*, Kohji Nishida{ddagger}, Yoshiro Kobayashi{dagger} and Teruo Okano2,*

* Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, Tokyo, Japan; {dagger} Division of Molecular Medicine, Department of Biomolecular Science, Toho University, Chiba, Japan; and {ddagger} Department of Ophthalmology and Visual Science, Tohoku University Graduate School of Medicine, Miyagi, Japan

With significant attention paid to the field of tissue-specific stem cells, the identification of stem cell-specific markers is of considerable importance. Previously, the side population (SP) phenotype, with the capacity to efflux the DNA-binding dye Hoechst 33342, has been recognized as a common feature of adult tissue-specific stem cells. In this study, we show that high expression of integrin beta3 (CD61) is an attribute of SP cells isolated from mouse bone marrow. Additionally, we confirmed that the expression of integrin beta3 is correlated with properties of quiescent hemopoietic stem cells (HSCs) including the strength of the SP phenotype, cell cycle arrest, expression of HSC markers, and long-term hemopoiesis. Importantly, Lineage (Lin)/integrin beta3high (beta3high) SP cells have as strong a capacity for long-term hemopoiesis as c-Kit+/Sca-1+/Lin SP cells, which are regarded as one of the most highly enriched HSC populations. Finally, the integrin beta3 subunit that is present in SP cells having the properties of HSCs, is associated with integrin {alpha}v (CD51). Therefore, our results demonstrate that high expression of integrin beta3 is correlated to the properties of quiescent HSCs and suggest that the integrin beta3 subunit is available as a common surface marker of tissue-specific stem cells.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported in part by the Center of Excellence Program for the 21st Century and the High-Tech Research Center Program, from the Ministry of Education, Culture, Sports, Science, and Technology, Japan; the Core Research for Evolution Science and Technology Program by the Japan Science and Technology Agency; and the Core to Core Program from the Japan Society for the Promotion of Science.

2 Address correspondence and reprint requests to Dr. Teruo Okano, Institute of Advanced Biomedical Engineering and Science, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. E-mail address: tokano{at}abmes.twmu.ac.jp

3 Abbreviations used in this paper: SP, side population; NSP, non-SP; ABCG2, ATP-binding cassette transporter G2; HSC, hemopoietic stem cell; PY, pyronin Y; Lin, lineage.




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