Primitive macrophages control HSPC mobilization and definitive haematopoiesis
Primitive macrophages control HSPC mobilization and definitive haematopoiesis
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DOI：
10.1038/ncomms7227
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发表时间：
2015-02-01
影响因子：
16.6
通讯作者：
Kissa, Karima
中科院分区：
文献类型：
--
作者：
Travnickova, Jana;Vanessa Tran Chau;Kissa, Karima
在脊椎动物中，造血干/祖细胞（HSPC）首先出现在生殖腺-性腺-中肾（AGM）中，然后定殖于暂时性的并且随后为永久性的造血器官，从而允许整个成年生活中的造血。在这里，我们发现了一个意想不到的原始巨噬细胞群体，聚集在人类胚胎背主动脉周围的背肠系膜中胚层中，并研究了它在透明斑马鱼胚胎中的功能。我们的研究揭示了HSPCs和原始巨噬细胞在AGM中发生的动态相互作用。巨噬细胞的特异性化学和诱导性遗传耗竭或基质金属蛋白酶（Mmps）的抑制导致HSPC在AGM中的积累和造血器官定植的减少。最后，体内酶谱法证实了原始巨噬细胞在细胞外基质降解中的功能，这允许HSPC迁移通过AGM基质，它们的内渗，导致造血器官的定殖和永久性造血的建立。
In vertebrates, haematopoietic stem/progenitor cells (HSPCs) first emerge in the aorta-gonad-mesonephros (AGM) before colonizing transitory and subsequently definitive haematopoietic organs allowing haematopoiesis throughout adult life. Here we identify an unexpected primitive macrophage population accumulated in the dorsal mesenteric mesoderm surrounding the dorsal aorta of the human embryo and study its function in the transparent zebrafish embryo. Our study reveals dynamic interactions occurring between the HSPCs and primitive macrophages in the AGM. Specific chemical and inducible genetic depletion of macrophages or inhibition of matrix metalloproteinases (Mmps) leads to an accumulation of HSPCs in the AGM and a decrease in the colonization of haematopoietic organs. Finally, in vivo zymography demonstrates the function of primitive macrophages in extracellular matrix degradation, which allows HSPC migration through the AGM stroma, their intravasation, leading to the colonization of haematopoietic organs and the establishment of definitive haematopoiesis.