Extended Data Fig. 10: The proposed model of the IRF8-dose dependent myeloid lineage choice.
From: A RUNX–CBFβ-driven enhancer directs the Irf8 dose-dependent lineage choice between DCs and monocytes
a, Schematic models of the phenotypes of three mouse strains devoid of the +56, +32 or –50 kb Irf8 enhancer. The models are described as in Extended Data Fig. 1. Phenotypes of WT and Irf8–/– mice are also displayed for comparison. b, Proposed model: The RUNX–CBFβ-driven Irf8 + 56 kb enhancer induces early IRF8 expression in myeloid progenitors. The +56 kb enhancer-mediated high IRF8 expression in myeloid progenitor cells is essential for the development of CDPs and cDC1s, whereas low IRF8 expression in myeloid progenitor cells preferentially induces monopoiesis. The absence of IRF8 expression leads to differentiation into neutrophils (Neu). The lineage choice is epigenetically determined in an IRF8 dose-dependent manner via cooperation or antagonism with other TFs to activate distinct sets of downstream enhancers. TFs, transcription factors.
