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C/EBP alpha deficiency results in hyperproliferation of hematopoietic progenitor cells and disrupts macrophage development in vitro and in vivo

  1. Author:
    Heath, V.
    Suh, H. C.
    Holman, M.
    Renn, K.
    Gooya, J. M.
    Parkin, S.
    Klarmann, K. D.
    Ortiz, M.
    Johnson, P.
    Keller, J.

  2. Author Address

    SAIC Frederick Inc, NCI, Basic Res Program, Sci Applicat Int Corp,Lab Prot Dynam & Signaling, Frederick, MD 20702 USA. Ctr Canc Res, Lab Mol Immunoregulat, NCI, Frederick, MD USA Keller, J, SAIC Frederick Inc, NCI, Basic Res Program, Sci Applicat Int Corp,Lab Prot Dynam & Signaling, Bldg 560,Rm 12-03, Frederick, MD 20702 USA
    1. Year: 2004
    2. Date: SEP 15
  2. Journal: Blood
    1. 104
    2. 6
    3. Pages: 1639-1647
  4. Type of Article: Article
  1. Abstract:

    CCAAT enhancer binding protein-alpha (C/ EBPalpha) inhibits proliferation in multiple cell types; therefore, we evaluated whether C/EBPalpha-deficient hematopoietic progenitor cells (HPCs) have an increased proliferative potential in vitro and in vivo. In this study we demonstrate that C/EBPalpha(-/-) 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/EBPalpha(-/-) FL, whereas multipotential progenitors are unaffected. HGF-dependent progenitor cell lines can be derived by directly culturing C/EBPalpha(-/-) FL cells in vitro. Hyperproliferative spleen colonies and myelodysplastic syndrome (MDS) are observed in mice reconstituted with C/EBPalpha(-/-) FL cells, indicating progenitor hyperproliferation in vitro and in vivo. C/EBPalpha(-/-) FL lacked macrophage progenitors in vitro and had impaired ability to generate macrophages in vivo. These findings show that C/EBPalpha(-/-) 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. (C) 2004 by The American Society of Hematology

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  1. View record in Web of Science®
  2. WOS: 000223818600016

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