Developmental control of macrophage function

The combination between novel fate-mapping tools and single-cell RNA-sequencing technology has revealed the presence of multiple macrophage progenitors. This raises the fascinating possibility that what was once perceived as immense functional plasticity of macrophages could in fact come down to separate macrophage subsets performing distinct functions because of their differential cellular origin. The question of macrophage plasticity versus macrophage heterogeneity is broader than the difference between macrophages of embryonic or adult hematopoietic origin and is particularly relevant in the context of inflammation. In this manuscript, we review the potential impact of cellular origin on the function of macrophages. We also highlight the need for novel 'functional fate-mapping' tools that would reveal the history of the functional state of macrophages, rather than their cellular origin, in order to finally study their true plasticity in vivo.