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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 (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 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. R Search for Related Content PubMed PubMed Citation Articles by Heath, V. Articles by Keller, J. R Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 19, 2003 Accepted March 26, 2004 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 R Keller* Laboratory of Protein Dynamics and Signaling, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA Basic Research Program, SAIC-Frederick, Inc., Center for Cancer Research, National Cancer Institute, Frederick, MD, USA Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA * Corresponding author; email: kellerj{at}mail.ncifcrf.gov. C/EBP inhibits proliferation in multiple cell types, therefore, we evaluated whether C/EBP deficient hematopoietic progenitor cells (HPC) 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 increased self-renewal capacity in response to hematopoietic growth factors (HGF). There are fewer committed bi-potential progenitors in C/EBP-/- FL, while multi-potential 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 HPC and a block in the ability of multipotential progenitors to differentiate into bi-potential granulocyte/macrophage progenitors and their progeny. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Kandilci and G. C. Grosveld Reintroduction of CEBPA in MN1-overexpressing hematopoietic cells prevents their hyperproliferation and restores myeloid differentiation Blood, August 20, 2009; 114(8): 1596 - 1606. [Abstract] [Full Text] [PDF] 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. 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