Specification of tissue-resident macrophages during organogenesis
Specification of tissue-resident macrophages during organogenesis
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DOI：
10.1126/science.aaf4238
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发表时间：
2016-09-09
期刊：
影响因子：
56.9
通讯作者：
Geissmann, Frederic
中科院分区：
文献类型：
--
作者：
Mass, Elvira;Ballesteros, Ivan;Geissmann, Frederic
组织内巨噬细胞支持胚胎发育和组织稳态和修复。控制它们分化的机制尚不清楚。我们在这里报道，小鼠的红髓祖细胞产生巨噬前细胞（pMacs），从胚胎第9.5天开始，以趋化因子受体依赖的方式同时定植整个胚胎。随着转录调控因子在早期巨噬细胞中的表达具有组织特异性，pMacs启动的核心巨噬细胞程序迅速多样化。这一过程似乎对巨噬细胞的分化和维持至关重要，因为Id3的失活会损害肝巨噬细胞的发育，并导致成人选择性库普弗细胞缺乏症。我们认为巨噬细胞分化是器官发生的一个组成部分，因为pMacs定植器官胶原后，它们被指定为组织巨噬细胞，从而产生了在出生后组织中观察到的巨噬细胞多样性。
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 in mice generate premacrophages (pMacs) that simultaneously colonize the whole embryo from embryonic day 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.