C-Myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages.
C-Myb(+) erythro-myeloid progenitor-derived fetal monocytes give rise to adult tissue-resident macrophages.
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DOI：
10.1016/j.immuni.2015.03.011
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发表时间：
2015-04-21
期刊：
影响因子：
32.4
通讯作者：
Ginhoux F
中科院分区：
文献类型：
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作者：
Hoeffel G;Chen J;Lavin Y;Low D;Almeida FF;See P;Beaudin AE;Lum J;Low I;Forsberg EC;Poidinger M;Zolezzi F;Larbi A;Ng LG;Chan JK;Greter M;Becher B;Samokhvalov IM;Merad M;Ginhoux F
虽然被归类为造血细胞，但组织驻留巨噬细胞 (MF) 源自胚胎前体，它们在出生前播种到组织中，以产生自我更新的细胞群，该细胞群的维持独立于成年造血作用。在这里，我们使用子宫内 MF 耗竭策略以及卵黄囊 (YS) 和胎儿肝脏 (FL) 造血的命运图谱揭示了这些胚胎前体的身份。我们发现 YS MF 是小胶质细胞的主要前体，而大多数其他 MF 源自胎儿单核细胞 (MO)。 YS MF 和胎儿 MO 均源自 YS 中产生的红骨髓祖细胞 (EMP)。在YS中，EMP产生没有单核中间体的MF，而EMP在建立血液循环后播种FL，获得c-Myb表达并产生胎儿MO，然后播种胚胎组织并分化为MF。因此，由造血干细胞独立的胚胎前体建立的成体组织驻留 MF 源自两个不同的发育程序。
Although classified as hematopoietic cells, tissue- resident macrophages (MFs) arise from embryonic precursors that seed the tissues prior to birth to generate a self-renewing population, which is maintained independently of adult hematopoiesis. Here we reveal the identity of these embryonic precursors using an in utero MF-depletion strategy and fate-mapping of yolk sac (YS) and fetal liver (FL) hematopoiesis. We show that YS MFs are the main precursors of microglia, while most other MFs derive from fetal monocytes (MOs). Both YS MFs and fetal MOs arise from erythro-myeloid progenitors (EMPs) generated in the YS. In the YS, EMPs gave rise to MFs without monocytic intermediates, while EMP seeding the FL upon the establishment of blood circulation acquired c-Myb expression and gave rise to fetal MOs that then seeded embryonic tissues and differentiated into MFs. Thus, adult tissue- resident MFs established from hematopoietic stem cell-independent embryonic precursors arise from two distinct developmental programs.