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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2446-2454. Prepublished online as a Blood First Edition Paper on June 6, 2006; DOI 10.1182/blood-2006-02-002204. This Article Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2006-02-002204v1 108/7/2446    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 Yahata, T. Articles by Ando, K. Search for Related Content PubMed PubMed Citation Articles by Yahata, T. Articles by Ando, K. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 8, 2006 Accepted May 20, 2006 Clonal analysis of thymus-repopulating cells presents direct evidence for self-renewal division of human hematopoietic stem cells Takashi Yahata, Shizu Yumino, Yin Seng, Hiroko Miyatake, Tomoko Uno, Yukari Muguruma, Mamoru Ito, Hiroyuki Miyoshi, Shunichi Kato, Tomomitsu Hotta, and Kiyoshi Ando* Division of Hematopoiesis, Tokai University School of Medicine, Kanagawa, Japan Central Institute of Experimental Animals, Kawasaki, Kanagawa, Japan BioResource Center, RIKEN Tsukuba Institute, Tsukuba, Ibaraki, Japan Tokai University School of Medicine, Isehara, Kanagawa, Japan * Corresponding author; email: andok{at}keyaki.cc.u-tokai.ac.jp. To elucidate the in vivo kinetics of human hematopoietic stem cells (HSCs), CD34+CD38- cells were infected with lentivirus vector and transplanted into immunodeficient mice. We analyzed the multilineage differentiation and self-renewal abilities of individual thymus-repopulating clones in primary recipients, and their descending clones paired secondary recipients, by tracing lentivirus gene integration sites in each lymphomyeloid progeny using a linear amplification-mediated PCR strategy. Our clonal analysis revealed that a single human thymus-repopulating cell had the ability to produce lymphoid and myeloid lineage cells in primary recipient and each secondary recipient, indicating that individual human HSCs expand clonally by self-renewal division. Furthermore, we found that the proportion of HSC clones present in the CD34+ cell population decreased as HSCs replicated during extensive repopulation and also as the differentiation capacity of the HSC clones became limited. This indicates the restriction of the ability of individual HSCs despite the expansion of total HSC population. We also demonstrated that the extensive self-renewal potential was confined in the relatively small proportion of HSC clones. We conclude that our clonal tracking studies clearly demonstrated that heterogeneity in the self-renewal capacity of HSC clones underlies the differences in clonal longevity in the CD34+ stem cell pool. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. S. Kahl New Therapeutic Strategies for Mantle Cell Lymphoma ASCO Educational Book, January 1, 2008; 2008(1): 392 - 397. [Abstract] [Full Text] [PDF]

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