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This Article Full Text Full Text (PDF) 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 Solar, G. P. Articles by Eaton, D. L. Search for Related Content PubMed PubMed Citation Articles by Solar, G. P. Articles by Eaton, D. L. Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Role of c-mpl in Early Hematopoiesis Gregg P. Solar, William G. Kerr, Francis C. Zeigler, Darren Hess, Christopher Donahue, Frederic J. de Sauvage, and Dan L. Eaton From the Departments of Cardiovascular Research, Molecular Oncology and Flow Cytometry, Genentech Inc, South San Francisco, CA; and the Department of Molecular and Cellular Engineering, Institute for Human Gene Therapy, University of Pennsylvania, Philadelphia. Recently, several lines of evidence have indicated an expanded role for thrombopoietin (TPO) and its receptor, c-mpl, in hematopoiesis. In addition to being the primary physiological regulator of platelet production, it is now apparent that TPO also acts during early hematopoiesis. To futher define the role of TPO in early hematopoiesis we have identified discrete murine and human stem cell populations with respect to c-mpl expression and evaluated their potential for hematopoietic engraftment. Fluorescence-activated cell sorter analysis of enriched stem cell populations showed the presence of c-mpl expressing subpopulations. Approximately 50% of the murine fetal liver stem cell-enriched population, AA4+Sca+c-kit+, expressed c-mpl. Analysis of the murine marrow stem cell population LinloSca+c-kit+ showed that 70% of this population expressed c-mpl. Expression of c-mpl was also detected within the human bone marrow CD34+CD38 stem cell progenitor pool and approximately 70% of that population expressed c-mpl. To rigorously evaluate the role of TPO/c-mpl in early hematopoiesis we compared the repopulation capacity of murine stem cell populations with respect to c-mpl expression in a competitive repopulation assay. When comparing the fetal liver progenitor populations, AA4+Sca+c-kit+c-mpl+ and AA4+Sca+c-kit+c-mpl, we found that stem cell activity segregates with c-mpl expression. This result is complemented by the observation that the LinloSca+ population of c-mpl gene-deficient mice was sevenfold less potent than LinloSca+ cells from wild-type mice in repopulating activity. The engraftment potential of the human CD34+CD38c-mpl+ population was evaluated in a severe combined immunodeficient-human bone model. In comparison to the CD34+ CD38c-mpl population, the CD34+CD38c-mpl+ cells showed significantly better engraftment. These results demonstrate a physiological role for TPO and its receptor, c-mpl, in regulating early hematopoiesis. Blood, Vol. 92 No. 1 (July 1), 1998: pp. 4-10 © 1998 by The American Society of Hematology. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: H. O. Lee, J. M. Davidson, and R. J. Duronio Endoreplication: polyploidy with purpose Genes & Dev., November 1, 2009; 23(21): 2461 - 2477. [Abstract] [Full Text] [PDF] S. N. Constantinescu Mpl and thrombocytosis: levels matter Blood, February 19, 2009; 113(8): 1617 - 1618. [Full Text] [PDF] B. J. Lannutti, A. Epp, J. Roy, J. Chen, and N. C. 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