| First Author | Wölfler A | Year | 2010 |
| Journal | Blood | Volume | 116 |
| Issue | 20 | Pages | 4116-25 |
| PubMed ID | 20807890 | Mgi Jnum | J:166620 |
| Mgi Id | MGI:4848257 | Doi | 10.1182/blood-2010-03-275404 |
| Citation | Wolfler A, et al. (2010) Lineage-instructive function of C/EBPalpha in multipotent hematopoietic cells and early thymic progenitors. Blood 116(20):4116-25 |
| abstractText | Hematopoiesis is tightly controlled by transcription regulatory networks, but how and when specific transcription factors control lineage commitment are still largely unknown. Within the hematopoietic stem cell (Lin(-)Sca-1(+)c-Kit(+)) compartment these lineage-specific transcription factors are expressed at low levels but are up-regulated with the process of lineage specification. CCAAT/enhancer binding protein alpha (C/EBPalpha) represents one of these factors and is involved in myeloid development and indispensable for formation of granulocytes. To track the cellular fate of stem and progenitor cells, which express C/EBPalpha, we developed a mouse model expressing Cre recombinase from the Cebpa promoter and a conditional EYFP allele. We show that Cebpa/EYFP(+) cells represent a significant subset of multipotent hematopoietic progenitors, which predominantly give rise to myeloid cells in steady-state hematopoiesis. C/EBPalpha induced a strong myeloid gene expression signature and down-regulated E2A-induced regulators of early lymphoid development. In addition, Cebpa/EYFP(+) cells compose a fraction of early thymic progenitors with robust myeloid potential. However, Cebpa/EYFP(+) multipotent hematopoietic progenitors and early thymic progenitors retained the ability to develop into erythroid and T-lymphoid lineages, respectively. These findings support an instructive but argue against a lineage-restrictive role of C/EBPalpha in multipotent hematopoietic and thymic progenitors. |
