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Blood, 15 April 2005, Vol. 105, No. 8, pp. 3109-3116. Prepublished online as a Blood First Edition Paper on December 21, 2004; DOI 10.1182/blood-2004-05-1773. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-05-1773v1 105/8/3109    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 Srour, E. F. Articles by Orschell, C. M. Search for Related Content PubMed PubMed Citation Articles by Srour, E. F. Articles by Orschell, C. M. Related Collections Hematopoiesis and Stem Cells Cell Cycle Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Modulation of in vitro proliferation kinetics and primitive hematopoietic potential of individual human CD34+CD38–/lo cells in G0 Edward F. Srour, Xia Tong, Ki Woong Sung, P. Artur Plett, Susan Rice, Joanne Daggy, Constantin T. Yiannoutsos, Rafat Abonour, and Christie M. Orschell From the Division of Hematology/Oncology, Department of Medicine, Department of Pediatrics, Herman B Wells Center for Pediatric Research, Department of Microbiology/Immunology, Indiana University Cancer Center, and Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN. Whether cytokines can modulate the fate of primitive hematopoietic progenitor cells (HPCs) through successive in vitro cell divisions has not been established. Single human marrow CD34+CD38–/lo cells in the G0 phase of cell cycle were cultured under 7 different cytokine combinations, monitored for proliferation on days 3, 5, and 7, then assayed for long-term culture-initiating cell (LTC-IC) function on day 7. LTC-IC function was then retrospectively correlated with prior number of in vitro cell divisions to determine whether maintenance of LTC-IC function after in vitro cell division is dependent on cytokine exposure. In the presence of proliferation progression signals, initial cell division was independent of cytokine stimulation, suggesting that entry of primitive HPCs into the cell cycle is a stochastic property. However, kinetics of proliferation beyond day 3 and maintenance of LTC-IC function were sensitive to cytokine stimulation, such that LTC-IC underwent an initial long cell cycle, followed by more synchronized shorter cycles varying in length depending on the cytokine combination. Nonobese diabetic/severe combined immunodeficiency (NOD/SCID) transplantation studies revealed analogous results to those obtained with LTC-ICs. These data suggest that although exit from quiescence and commitment to proliferation might be stochastic, kinetics of proliferation, and possibly fate of primitive HPCs, might be modulated by extrinsic factors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Noda, K. Horiguchi, H. Ichikawa, and H. Miyoshi Repopulating Activity of Ex Vivo-Expanded Murine Hematopoietic Stem Cells Resides in the CD48-c-Kit+Sca-1+Lineage Marker- Cell Population Stem Cells, March 1, 2008; 26(3): 646 - 655. [Abstract] [Full Text] [PDF] M. A. Dao and J. A. Nolta Cytokine and integrin stimulation synergize to promote higher levels of GATA-2, c-myb, and CD34 protein in primary human hematopoietic progenitors from bone marrow Blood, March 15, 2007; 109(6): 2373 - 2379. [Abstract] [Full Text] [PDF] S. Gottschling, R. Saffrich, A. Seckinger, U. Krause, K. Horsch, K. Miesala, and A. D. Ho Human Mesenchymal Stromal Cells Regulate Initial Self-Renewing Divisions of Hematopoietic Progenitor Cells by a {beta}1-Integrin-Dependent Mechanism Stem Cells, March 1, 2007; 25(3): 798 - 806. [Abstract] [Full Text] [PDF] B. Dykstra, J. Ramunas, D. Kent, L. McCaffrey, E. Szumsky, L. Kelly, K. Farn, A. Blaylock, C. Eaves, and E. Jervis High-resolution video monitoring of hematopoietic stem cells cultured in single-cell arrays identifies new features of self-renewal PNAS, May 23, 2006; 103(21): 8185 - 8190. [Abstract] [Full Text] [PDF] X. Yu, J. K. Alder, J. H. Chun, A. D. Friedman, S. Heimfeld, L. Cheng, and C. I. Civin HES1 Inhibits Cycling of Hematopoietic Progenitor Cells via DNA Binding Stem Cells, April 1, 2006; 24(4): 876 - 888. [Abstract] [Full Text] [PDF]

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