Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors.

Tissue-resident macrophages originate from yolk-sac-derived erythro-myeloid progenitors.
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DOI:
10.1038/nature13989
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发表时间:
2015-02-26
期刊:
影响因子:
64.8
通讯作者:
Rodewald HR
Rodewald HR
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Gomez Perdiguero E;Klapproth K;Schulz C;Busch K;Azzoni E;Crozet L;Garner H;Trouillet C;de Bruijn MF;Geissmann F;Rodewald HR

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Most haematopoietic cells renew from adult haematopoietic stem cells (HSCs),,, however, macrophages in adult tissues can self-maintain independently of HSCs,,,. Progenitors with macrophage potentialin vitrohave been described in the yolk sac before emergence of HSCs,,,,,, and fetal macrophages,,can develop independently ofMyb, a transcription factor required for HSC, and can persist in adult tissues,,. Nevertheless, the origin of adult macrophages and the qualitative and quantitative contributions of HSC and putative non-HSC-derived progenitors are still unclear. Here we show in mice that the vast majority of adult tissue-resident macrophages in liver (Kupffer cells), brain (microglia), epidermis (Langerhans cells) and lung (alveolar macrophages) originate from aTie2+(also known asTek) cellular pathway generatingCsf1r+erythro-myeloid progenitors (EMPs) distinct from HSCs. EMPs develop in the yolk sac at embryonic day (E) 8.5, migrate and colonize the nascent fetal liver before E10.5, and give rise to fetal erythrocytes, macrophages, granulocytes and monocytes until at least E16.5. Subsequently, HSC-derived cells replace erythrocytes, granulocytes and monocytes. Kupffer cells, microglia and Langerhans cells are only marginally replaced in one-year-old mice, whereas alveolar macrophages may be progressively replaced in ageing mice. Our fate-mapping experiments identify, in the fetal liver, a sequence of yolk sac EMP-derived and HSC-derived haematopoiesis, and identify yolk sac EMPs as a common origin for tissue macrophages.
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