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Blood, 15 September 2004, Vol. 104, No. 6, pp. 1639-1647. Prepublished online as a Blood First Edition Paper on April 8, 2004; DOI 10.1182/blood-2003-11-3963. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-11-3963v1 104/6/1639    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 Heath, V. Articles by Keller, J. Search for Related Content PubMed PubMed Citation Articles by Heath, V. Articles by Keller, J. Related Collections Hematopoiesis and Stem Cells Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS C/EBP deficiency results in hyperproliferation of hematopoietic progenitor cells and disrupts macrophage development in vitro and in vivo Victoria Heath, Hyung Chan Suh, Matthew Holman, Katie Renn, John M. Gooya, Sarah Parkin, Kimberly D. Klarmann, Mariaestela Ortiz, Peter Johnson, and Jonathan Keller From the Laboratory of Protein Dynamics and Signaling, Science Applications International Corporation (SAIC)-Frederick, Inc, Frederick, MD; the Basic Research Program, SAIC-Frederick, Inc, Frederick, MD; and the Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute-Frederick, Frederick, MD. CCAAT enhancer binding protein- (C/EBP) inhibits proliferation in multiple cell types; therefore, we evaluated whether C/EBP-deficient hematopoietic progenitor cells (HPCs) have an increased proliferative potential in vitro and in vivo. In this study we demonstrate that C/EBP-/- fetal liver (FL) progenitors are hyperproliferative, show decreased differentiation potential, and show increased self-renewal capacity in response to hematopoietic growth factors (HGFs). There are fewer committed bipotential progenitors in C/EBP-/- FL, whereas multipotential progenitors are unaffected. HGF-dependent progenitor cell lines can be derived by directly culturing C/EBP-/- FL cells in vitro Hyperproliferative spleen colonies and myelodysplastic syndrome (MDS) are observed in mice reconstituted with C/EBP-/- FL cells, indicating progenitor hyperproliferation in vitro and in vivo. C/EBP-/- FL lacked macrophage progenitors in vitro and had impaired ability to generate macrophages in vivo. These findings show that C/EBP deficiency results in hyperproliferation of HPCs and a block in the ability of multipotential progenitors to differentiate into bipotential granulocyte/macrophage progenitors and their progeny. (Blood. 2004; 104:1639-1647) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. S. Hasemann, I. Damgaard, M. B. Schuster, K. Theilgaard-Monch, A. B. Sorensen, A. Mrsic, T. Krugers, B. Ylstra, F. S. Pedersen, C. Nerlov, et al. Mutation of C/EBP{alpha} predisposes to the development of myeloid leukemia in a retroviral insertional mutagenesis screen Blood, April 15, 2008; 111(8): 4309 - 4321. [Abstract] [Full Text] [PDF] T. Akagi, T. Saitoh, J. O'Kelly, S. Akira, A. F. Gombart, and H. P. Koeffler Impaired response to GM-CSF and G-CSF, and enhanced apoptosis in C/EBP{beta}-deficient hematopoietic cells Blood, March 15, 2008; 111(6): 2999 - 3004. [Abstract] [Full Text] [PDF] C. 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