Macrophages are one of the most diverse cell populations in terms of their anatomical location and functional specialization during both homeostasis and disease. Although it has been shown in different fate mapping models that some macrophages present in adult tissues are already established during fetal development, their exact origins are still under debate. In the current study, we developed a fate mapping strain, based on the Kit locus, which allowed us to readdress "the origins" question. Different types of macrophages from various adult tissues were traced to their fetal or adult sources by inducing labeling in precursors at several time points either during fetal development or in adult mice. We show that all adult macrophages, resident or infiltrating, are progenies of classical hematopoietic stem cells (HSC) with the exception of microglia and, partially epidermal Langerhans cells, which are yolk sac (YS)-derived. Most resident macrophages originate from fetal sources and then self-renew in situ to maintain their numbers through the lifetime of the mouse. Karjalainen and colleagues show here that most resident macrophages, brain microglia excluded, are descendants of fetal hematopoietic stem cells and not from yolk sac precursors as suggested previously.
Sheng, J., Ruedl, C., & Karjalainen, K. (2015). Most Tissue-Resident Macrophages Except Microglia Are Derived from Fetal Hematopoietic Stem Cells. Immunity, 43(2), 382–393. https://doi.org/10.1016/j.immuni.2015.07.016