The mechanisms that control the diversification of tissue-resident macrophages remain unclear. In Science, Geissmann and colleagues perform spatio-temporal analysis of macrophage development in mice. Transcriptional profiling of embryonic erythro-myeloid progenitors, fetal CD45+Lin−c-kit− pre-macrophages and F4/80+ adult tissue macrophages identifies a core macrophage transcriptional program, including expression of the transcription-factor-encoding genes Csf1r, Maf, Batf3, Pparg, Irf8 and Zeb2, that is acquired in pre-macrophages as they colonize the embryo in a manner dependent on the chemokine receptor CX3CR1. Tissue-specific signatures are acquired in each population as early as embryonic day 12.5 in microglia, Kupffer cells and kidney macrophages or undergo postnatal changes in Langerhans cells and alveolar macrophages. Genes encoding some tissue-specific factors are expressed as early as embryonic day 10.26 in tissue macrophages (Sall1 and Sall3) or are expressed in erythro-myeloid progenitors or pre-macrophages (Id1 and Sall3) before their expression becomes restricted to a certain macrophage subset. The transcription factor Id3 emerges as being important for the development and maintenance of Kupffer cells.

Science (4 August 2016) doi:10.1126/science.aaf4238