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Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2003-05-1558. This Article 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 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 Social Bookmarking                   What's this? Submitted May 20, 2003 Accepted September 10, 2003 Lentivector-mediated clonal tracking reveals intrinsic heterogeneity in the human hematopoietic stem cell compartment and culture-induced stem cell impairment Frederic Mazurier, Olga I Gan, Joby L McKenzie, Monica Doedens, and John E Dick* Division of Cell and Molecular Biology, University Health Network, Toronto, ON, Canada; Department of Medical Genetics and Microbiology, University of Toronto, Toronto, ON, Canada * Corresponding author; email: jdick{at}uhnres.utoronto.ca. Knowledge of the composition and inter-relationship of the various hematopoietic stem cells (HSC) that comprise the human HSC pool and the consequence of culture on each class are required for effective stem cell-based therapies. Clonal tracking of retrovirally transduced HSC in NOD/SCID mice revealed heterogeneity in the repopulation capacity of SCID-repopulating cells (SRC). 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 SRC. Here, we report establishment of a clonal tracking method that utilizes lentivectors to transduce HSC with minimal manipulation during overnight culture without cytokine stimulation. By serial bone marrow (BM) sampling of transplanted mice, short-term SRC (ST-SRC) and long-term SRC (LT-SRC) were identified based on repopulation dynamics demonstrating that their existence is not an experimental artifact but reflects the state of the HSC pool. However, 4 day culture in conditions previously used for SRC retroviral transduction did significantly reduce SRC number as assessed by clonal analysis. These studies provide a foundation to determine the molecular and cellular determinants of human HSC development and to develop therapies targeted to specific HSC classes. 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