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PMID:15073037

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Citation

Heath, V, Suh, HC, Holman, M, Renn, K, Gooya, JM, Parkin, S, Klarmann, KD, Ortiz, M, Johnson, P and Keller, J (2004) C/EBPalpha deficiency results in hyperproliferation of hematopoietic progenitor cells and disrupts macrophage development in vitro and in vivo. Blood 104:1639-47

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.

Links

PubMed Online version:10.1182/blood-2003-11-3963

Keywords

Animals; CCAAT-Enhancer-Binding Protein-alpha/deficiency; CCAAT-Enhancer-Binding Protein-alpha/genetics; CCAAT-Enhancer-Binding Protein-alpha/metabolism; Cell Differentiation/drug effects; Cell Division/drug effects; Cell Transplantation; Cells, Cultured; Gene Deletion; Gene Expression Regulation, Developmental; Hematopoietic Stem Cells/drug effects; Hematopoietic Stem Cells/metabolism; Hematopoietic Stem Cells/pathology; Hepatocyte Growth Factor/pharmacology; Interleukin-3/metabolism; Liver/embryology; Liver/metabolism; Liver/pathology; Macrophages/drug effects; Macrophages/metabolism; Macrophages/pathology; Mice; Mice, Knockout; Proto-Oncogene Proteins c-met/genetics; Proto-Oncogene Proteins c-met/metabolism; Survival Rate

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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