Hematopoietic stem cells (HSCs) are generated from specialized endothelial cells of the embryonic aorta. Inflammatory factors are implicated in regulating mouse HSC development, but which cells in the aorta-gonad-mesonephros (AGM) microenvironment produce these factors is unknown. In the adult, macrophages play both pro- and anti-inflammatory roles. We sought to examine whether macrophages or other hematopoietic cells found in the embryo prior to HSC generation were involved in the AGM HSC-generative microenvironment. CyTOF analysis of CD45+ AGM cells revealed predominance of two hematopoietic cell types, mannose-receptor positive macrophages and mannose-receptor negative myeloid cells. We show here that macrophage appearance in the AGM was dependent on the chemokine receptor Cx3cr1. These macrophages expressed a pro-inflammatory signature, localized to the aorta, and dynamically interacted with nascent and emerging intra-aortic hematopoietic cells (IAHCs). Importantly, upon macrophage depletion, no adult-repopulating HSCs were detected, thus implicating a role for pro-inflammatory AGM-associated macrophages in regulating the development of HSCs.

中文翻译：

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促炎性主动脉相关的巨噬细胞参与造血干细胞的胚胎发育。

造血干细胞（HSC）由胚胎主动脉的专门内皮细胞生成。炎症因子参与调节小鼠HSC的发育，但是主动脉-性腺-中肾（AGM）微环境中的哪些细胞会产生这些因子尚不清楚。在成年人中，巨噬细胞同时发挥促炎和抗炎作用。我们试图检查在HSC产生之前在胚胎中发现的巨噬细胞或其他造血细胞是否参与了AGM HSC产生的微环境。CD45 + AGM细胞的CyTOF分析显示两种造血细胞占主导地位，即甘露糖受体阳性巨噬细胞和甘露糖受体阴性髓样细胞。我们在这里显示巨噬细胞在AGM中的出现取决于趋化因子受体Cx3cr1。这些巨噬细胞表达了促炎性信号，定位于主动脉，并与新生的和新兴的主动脉内造血细胞（IAHC）动态相互作用。重要的是，在巨噬细胞耗竭后，未检测到成年繁殖的HSC，因此与促炎性AGM相关的巨噬细胞在调节HSC的发育中起作用。