Figure 3. Molecular mechanisms by which niche-specific signals promote monocyte differentiation into different macrophage phenotypes (mice and humans).

Panel A. Niche specific signals induce the expression of lineage determining factors (LDTFs) that collaborate with core macrophage LDTFs to drive the selection of new enhancers. Pre-existing and new enhancers are further influenced by the actions of broadly expressed signal-dependent transcription factors that mediate the effects of internal and external signals.

Panel B. Sequence motifs enriched in Kupffer cell specific enhancers can enable inference of the transcription factors and upstream signaling pathways that drive differentiation from progenitor cells. For each motif, corresponding transcription factors, upstream signaling pathways, and sources of liver-specific signals are indicated.