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Prepublished online as a Blood First Edition Paper on October 24, 2002; DOI 10.1182/blood-2002-07-2051. This Article Full Text (PDF) All Versions of this Article: 2002-07-2051v1 101/5/1777    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kunisato, A. Articles by Hirai, H. Search for Related Content PubMed PubMed Citation Articles by Kunisato, A. Articles by Hirai, H. Social Bookmarking                   What's this? Submitted July 10, 2002 Accepted October 4, 2002 HES-1 preserves purified hematopoietic stem cells ex vivo and accumulates side population cells in vivo Atsushi Kunisato, Shigeru Chiba, Etsuko Nakagami-Yamaguchi, Keiki Kumano, Toshiki Saito, Shigeo Masuda, Tomoyuki Yamaguchi, Masatake Osawa, Ryoichiro Kageyama, Hiromitsu Nakauchi, Mitsuo Nishikawa, and Hisamaru Hirai* Departments of Hematology and Oncology, Graduate School of Medicine, and Cell Therapy and Transplantation Medicine, University of Tokyo Hospital, University of Tokyo, Tokyo, Japan Developmental Biology, Riken Center, Kobe, Japan Institute for Virus Research, Kyoto University, Kyoto, Japan Department of Immunology, Institute of Basic Medical Science, University of Tsukuba, Tsukuba, Japan Pharmaceutical Research Laboratory, Kirin Brewery Co., Takasaki, Japan * Corresponding author; email: hhirai-tky{at}umin.ac.jp. Mouse long-term hematopoietic reconstituting cells exist in the c-Kit+Sca-1+Lin- (KSL) cell population; among them, CD34low/- cells represent the most highly purified population of hematopoietic stem cells in the adult bone marrow. Here, we demonstrate that retrovirus-mediated transduction of CD34low/-c-Kit+Sca-1+Lin- (34-KSL) cells with the HES-1 gene, which encodes a basic helix-loop-helix transcription factor functioning downstream of the Notch receptor, and is a key molecule for the growth phase of neural stem cells in the embryo, preserves the long-term reconstituting activity of these cells in vitro. We also show that cells derived from the HES-1-transduced 34-KSL population produce progenies characterized by negative Hoechst-dye staining, which defines the side population, and by CD34low/- profile in the bone marrow KSL population in each recipient mouse at ratios 3.5 and 7.8-fold those produced by non-transduced 34-KSL-derived competitor cells. We conclude that HES-1 preserves the long-term reconstituting hematopoietic activity of 34-KSL stem cells ex vivo. Upregulation of HES-1 protein in the 34-KSL population before unnecessary cell division, i.e., without retrovirus transduction, may represent a potent approach to absolute expansion of hematopoietic stem cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. A. M. Akinci, H. Turner, M. Taveras, A. Barash, Z. Wang, P. Reinach, and J. M. Wolosin Molecular Profiling of Conjunctival Epithelial Side-Population Stem Cells: Atypical Cell Surface Markers and Sources of a Slow-Cycling Phenotype Invest. Ophthalmol. Vis. Sci., September 1, 2009; 50(9): 4162 - 4172. [Abstract] [Full Text] [PDF] N. P. Rodrigues, A. S. Boyd, C. Fugazza, G. E. May, Y. Guo, A. J. Tipping, D. T. Scadden, P. Vyas, and T. 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