Lineage-instructive function of C/EBPα in multipotent hematopoietic cells and early thymic progenitors
Blood , Volume 116 - Issue 20 p. 4116- 4125
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 α (C/EBPα) 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/EBPα, 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/EBPα 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/EBPα in multipotent hematopoietic and thymic progenitors.
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Wölfler, A, van Danen-van Oorschot, A.A, Haanstra, J.R, Valkhof, M, Bodner, C, Vroegindeweij, E.M, … Touw, I.P. (2010). Lineage-instructive function of C/EBPα in multipotent hematopoietic cells and early thymic progenitors. Blood, 116(20), 4116–4125. doi:10.1182/blood-2010-03-275404