| First Author | Heath V | Year | 2004 |
| Journal | Blood | Volume | 104 |
| Issue | 6 | Pages | 1639-47 |
| PubMed ID | 15073037 | Mgi Jnum | J:92958 |
| Mgi Id | MGI:3055255 | Doi | 10.1182/blood-2003-11-3963 |
| Citation | Heath V, et al. (2004) C/EBPalpha deficiency results in hyperproliferation of hematopoietic progenitor cells and disrupts macrophage development in vitro and in vivo. Blood 104(6):1639-47 |
| abstractText | 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. |
