First Author | Fukuchi Y | Year | 2006 |
Journal | EMBO J | Volume | 25 |
Issue | 14 | Pages | 3398-410 |
PubMed ID | 16858416 | Mgi Jnum | J:111172 |
Mgi Id | MGI:3653155 | Doi | 10.1038/sj.emboj.7601199 |
Citation | Fukuchi Y, et al. (2006) Comprehensive analysis of myeloid lineage conversion using mice expressing an inducible form of C/EBPalpha. EMBO J 25(14):3398-410 |
abstractText | CCAAT/enhancer-binding protein (C/EBP) alpha is a critical regulator for early myeloid differentiation. Although C/EBPalpha has been shown to convert B cells into myeloid lineage, precise roles of C/EBPalpha in various hematopoietic progenitors and stem cells still remain obscure. To examine the consequence of C/EBPalpha activation in various progenitors and to address the underlying mechanism of lineage conversion in detail, we established transgenic mice expressing a conditional form of C/EBPalpha. Using these mice, we show that megakaryocyte/erythroid progenitors (MEPs) and common lymphoid progenitors (CLPs) could be redirected to functional macrophages in vitro by a short-term activation of C/EBPalpha, and the conversion occurred clonally through biphenotypic intermediate cells. Moreover, in vivo activation of C/EBPalpha in mice led to the increase of mature granulocytes and myeloid progenitors with a concomitant decrease of hematopoietic stem cells and nonmyeloid progenitors. Our study reveals that C/EBPalpha can activate the latent myeloid differentiation program of MEP and CLP and shows that its global activation affects multilineage homeostasis in vivo. |