Role of early B cell factor 1 in HSPCs

Abstract

Early B cell factor 1 (Ebf1) is an essential transcription factor that orchestrates the B cell lineage program. Despite its heavily characterised role in the B cell lineage, it has been suggested that Ebf1 plays a role in the haematopoietic stem cell and progenitor compartment (HSPC). To gain further insight into the potential role of EBF1 in HSPCs we analysed the haematopoietic compartment of Ebf1fl/flTie2Cre conditional KO mice. We observed a modest increase in the number of HSCs in these mice and in order to test their HSC functionality we performed competitive adoptive transfers of Ebf1fl/flTie2Cre HSCs into WT recipients. Interestingly, we observed a decrease in chimerism in primary and secondary adoptive transfers from Ebf1fl/flTie2Cre HSCs compared to Ebf1wt/wtTie2Cre HSCs. Further analysis of Ebf1fl/flTie2Cre mice revealed a significant increase of myeloid-biased multipotent progenitors (MPP2/3) as well as mature cells of the myeloid compartment. Moreover, CFU-assays of Ebf1fl/flTie2Cre HSCs showed an increase in the number of myeloid colonies relative to Ebf1wt/wtTie2Cre HSCs. Together, these data demonstrate that loss of Ebf1 results in myeloid biased haematopoietic output and suggests that Ebf1 contributes to the regulation of HSC function.