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Blood, 1 August 2008, Vol. 112, No. 3, pp. 560-567. Prepublished online as a Blood First Edition Paper on May 27, 2008; DOI 10.1182/blood-2007-10-117820. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: blood-2007-10-117820v1 blood-2007-10-117820v2 112/3/560    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 Kent, D. G. Articles by Eaves, C. J. Search for Related Content PubMed PubMed Citation Articles by Kent, D. G. Articles by Eaves, C. J. Related Collections Hematopoiesis and Stem Cells Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS AND STEM CELLS Steel factor coordinately regulates the molecular signature and biologic function of hematopoietic stem cells David G. Kent1,2, Brad J. Dykstra1,2, Jay Cheyne1, Elaine Ma1, and Connie J. Eaves1,2 1 Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, BC; and 2 Department of Medical Genetics, Medicine, and Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC Hematopoietic stem cells (HSCs) regenerated in vivo display sustained differences in their self-renewal and differentiation activities. Variations in Steel factor (SF) signaling are known to affect these functions in vitro, but the cellular and molecular mechanisms involved are not understood. To address these issues, we evaluated highly purified HSCs maintained in single-cell serum-free cultures containing 20 ng/mL IL-11 plus 1, 10, or 300 ng/mL SF. Under all conditions, more than 99% of the cells traversed a first cell cycle with similar kinetics. After 8 hours in the 10 or 300 ng/mL SF conditions, the frequency of HSCs remained unchanged. However, in the next 8 hours (ie, 6 hours before any cell divided), HSC integrity was sustained only in the 300 ng/mL SF cultures. The cells in these cultures also contained significantly higher levels of Bmi1, Lnk, and Ezh2 transcripts but not of several other regulators. Assessment of 21 first division progeny pairs further showed that only those generated in 300 ng/mL SF cultures contained HSCs and pairs of progeny with similar differentiation programs were not observed. Thus, SF signaling intensity can directly and coordinately alter the transcription factor profile and long-term repopulating ability of quiescent HSCs before their first division. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. Xu, S. Eleswarapu, H. Geiger, K. Szczur, D. Daria, Y. Zheng, J. Settleman, E. F. Srour, D. A. Williams, and M.-D. Filippi Loss of the Rho GTPase activating protein p190-B enhances hematopoietic stem cell engraftment potential Blood, October 22, 2009; 114(17): 3557 - 3566. [Abstract] [Full Text] [PDF] D. G. Kent, M. R. Copley, C. Benz, S. Wohrer, B. J. Dykstra, E. Ma, J. Cheyne, Y. Zhao, M. B. Bowie, Y. Zhao, et al. Prospective isolation and molecular characterization of hematopoietic stem cells with durable self-renewal potential Blood, June 18, 2009; 113(25): 6342 - 6350. [Abstract] [Full Text] [PDF] J. E. Dick Stem cell concepts renew cancer research Blood, December 15, 2008; 112(13): 4793 - 4807. [Abstract] [Full Text] [PDF]

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