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Sheng, Ruedl, and Karjalainen published in Immunity (Sheng et al., 2015) a fatemapping model where the expression of Cre recombinase was inducible in Kit-expressing cells (Kit-MeriCreMer mice). In this system, the authors also revisited the origin of adult tissue-resident macrophages. For a long time, these macrophages have been assumed to be monocyte derivatives and hence ultimately to originate from adult bone marrow stem cells. In recent years, this view has been completely revised by the work of several groups (Schulz et al., 2012; Hashimoto et al., 2013), and in the field there is now a view that resident macrophages in most tissues do not arise from adult hematopoietic stem cells (HSCs) but rather develop at pre-natal stages and persist autonomously in adult tissues (at least under steady-state conditions). However, the precise cell of origin for tissue-resident macrophages during embryonic life (stages …