Research Article

Specification of tissue-resident macrophages during organogenesis

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Science  04 Aug 2016:
DOI: 10.1126/science.aaf4238

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Tissue-resident macrophages support embryonic development and tissue homeostasis and repair. The mechanisms that control their differentiation remain unclear. We report here that erythro-myeloid progenitors generate pre-macrophages (pMacs) that simultaneously colonize the whole embryo from embryonic day (E)9.5 in a chemokine-receptor dependent manner. The core macrophage program initiated in pMacs is rapidly diversified as expression of transcriptional regulators becomes tissue-specific in early macrophages. This process appears essential for macrophage specification and maintenance, as inactivation of Id3 impairs the development of liver macrophages and results in selective Kupffer cell deficiency in adults. We propose that macrophage differentiation is an integral part of organogenesis as colonization of organ anlagen by pMacs is followed by their specification into tissue macrophages, hereby generating the macrophage diversity observed in postnatal tissues.

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