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Blood, 18 June 2009, Vol. 113, No. 25, pp. 6342-6350. Prepublished online as a Blood First Edition Paper on April 17, 2009; DOI 10.1182/blood-2008-12-192054. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2008-12-192054v1 113/25/6342    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 CrossRef Google Scholar Articles by Kent, D. G. Articles by Eaves, C. J. PubMed PubMed Citation Articles by Kent, D. G. Articles by Eaves, C. J. Related Collections Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Prospective isolation and molecular characterization of hematopoietic stem cells with durable self-renewal potential David G. Kent1,2, Michael R. Copley1,2, Claudia Benz1, Stefan Wöhrer1, Brad J. Dykstra1, Elaine Ma1, John Cheyne1, Yongjun Zhao3, Michelle B. Bowie1, Yun Zhao1, Maura Gasparetto1, Allen Delaney3, Clayton Smith1,2, Marco Marra3, and Connie J. Eaves1,2 1 Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC; 2 University of British Columbia, Vancouver, BC; and 3 Michael Smith Genome Sciences Centre, British Columbia Cancer Agency, Vancouver, BC Hematopoietic stem cells (HSCs) are generally defined by their dual properties of pluripotency and extensive self-renewal capacity. However, a lack of experimental clarity as to what constitutes extensive self-renewal capacity coupled with an absence of methods to prospectively isolate long-term repopulating cells with defined self-renewal activities has made it difficult to identify the essential components of the self-renewal machinery and investigate their regulation. We now show that cells capable of repopulating irradiated congenic hosts for 4 months and producing clones of cells that can be serially transplanted are selectively and highly enriched in the CD150+ subset of the EPCR+CD48–CD45+ fraction of mouse fetal liver and adult bone marrow cells. In contrast, cells that repopulate primary hosts for the same period but show more limited self-renewal activity are enriched in the CD150– subset. Comparative transcriptome analyses of these 2 subsets with each other and with HSCs whose self-renewal activity has been rapidly extinguished in vitro revealed 3 new genes (VWF, Rhob, Pld3) whose elevated expression is a consistent and selective feature of the long-term repopulating cells with durable self-renewal capacity. These findings establish the identity of a phenotypically and molecularly distinct class of pluripotent hematopoietic cells with lifelong self-renewal capacity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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