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Blood, 15 January 2004, Vol. 103, No. 2, pp. 545-552. Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2003-05-1558. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-05-1558v1 103/2/545    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 Mazurier, F. Articles by Dick, J. E. Search for Related Content PubMed PubMed Citation Articles by Mazurier, F. Articles by Dick, J. E. Related Collections Hematopoiesis and Stem Cells Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Lentivector-mediated clonal tracking reveals intrinsic heterogeneity in the human hematopoietic stem cell compartment and culture-induced stem cell impairment Frédéric Mazurier, Olga I. Gan, Joby L. McKenzie, Monica Doedens, and John E. Dick From the Division of Cell and Molecular Biology, University Health Network, and Department of Molecular Genetics and Microbiology, University of Toronto, Toronto, ON, Canada. Knowledge of the composition and interrelationship of the various hematopoietic stem cells (HSCs) that comprise the human HSC pool and the consequence of culture on each class is required for effective therapies based on stem cells. Clonal tracking of retrovirally transduced HSCs in nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice revealed heterogeneity in the repopulation capacity of SCID-repopulating cells (SRCs). However, it is impossible to establish whether HSC heterogeneity is intrinsic or whether the culture conditions required for retroviral transduction induce qualitative and quantitative alterations to SRCs. Here, we report establishment of a clonal tracking method that uses lentivectors to transduce HSCs with minimal manipulation during overnight culture without cytokine stimulation. By serial bone marrow (BM) sampling of mice receiving transplants, short-term SRCs (ST-SRCs) and long-term SRCs (LT-SRCs) were identified on the basis of repopulation dynamics demonstrating that their existence is not an experimental artifact but reflects the state of the HSC pool. However, 4 days of culture in conditions previously used for SRC retroviral transduction significantly reduced SRC number as assessed by clonal analysis. These studies provide a foundation to understand the molecular and cellular determinants of human HSC development and to develop therapies targeted to specific HSC classes. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: O. Christ, K. Lucke, S. Imren, K. Leung, M. Hamilton, A. Eaves, C. Smith, and C. Eaves Improved purification of hematopoietic stem cells based on their elevated aldehyde dehydrogenase activity Haematologica, September 1, 2007; 92(9): 1165 - 1172. [Abstract] [Full Text] [PDF] Y.-W. Pan, J. M. Scarlett, T. T. Luoh, and P. Kurre Prolonged Adherence of Human Immunodeficiency Virus-Derived Vector Particles to Hematopoietic Target Cells Leads to Secondary Transduction In Vitro and In Vivo J. Virol., January 15, 2007; 81(2): 639 - 649. 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