Does niche competition determine the origin of tissue-resident macrophages?

Most tissue-resident macrophages are derived from embryonic precursors but, under certain circumstances, circulating monocytes can differentiate into self-maintaining tissue-resident macrophages that resemble their embryonic counterparts. In this Opinion article, we propose that distinct macrophage precursors have an almost identical potential to develop into resident macrophages but they compete for a restricted number of niches. The tight regulation of the niche ensures that monocytes do not differentiate into macrophages when the niche is full but that these cells can differentiate efficiently into macrophages when the niche is available. Imprinting by the niche would be the dominant factor conferring macrophage identity and self-maintenance capacity, rather than origin as was previously proposed.