Along with the aorta-gonad-mesonephros region, the head is a site of hematopoietic stem and progenitor cell (HS/PC) development in the mouse embryo. Macrophages are present in both these embryonic hemogenic sites and recent studies indicate a functional interaction of macrophages with hematopoietic cells as they are generated in the aorta. Whereas, brain macrophages or 'microglia' are known to affect neuronal patterning and vascular circuitry in the embryonic brain, it is unknown whether macrophages play a role in head hematopoiesis. Here we characterize head macrophages and examine whether they affect the HS/PC output of the hindbrain-branchial arch (HBA) region of the mouse embryo. We show that HBA macrophages are CD45+F4/80+CD11b+Gr1- and express the macrophage-specific Csf1r-GFP reporter. In the HBA of chemokine receptor deficient (Cx3cr1-/-) embryos, a reduction in erythropoiesis is concomitant with a decrease in HBA macrophage percentages. In cocultures, we show that head macrophages boost HPC numbers from HBA endothelial cells >2-fold, and that the pro-inflammatory factor TNFα is produced by head macrophages and influences HBA hematopoiesis in vitro. Taken together, head macrophages play a positive role in HBA erythropoiesis and HS/PC expansion and/or maturation, acting as micro-environmental cellular regulators in hematopoietic development.

中文翻译：

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巨噬细胞在胚胎头部造血中的作用

与主动脉-性腺-中肾区域一起，头部是小鼠胚胎中造血干细胞和祖细胞 (HS/PC) 发育的部位。巨噬细胞存在于这两个胚胎造血部位，最近的研究表明，巨噬细胞与造血细胞在主动脉中产生功能相互作用。虽然已知脑巨噬细胞或“小胶质细胞”会影响胚胎大脑中的神经元模式和血管回路，但巨噬细胞是否在头部造血中起作用尚不清楚。在这里，我们表征头部巨噬细胞并检查它们是否影响小鼠胚胎的后脑 - 分支弓 (HBA) 区域的 HS/PC 输出。我们显示 HBA 巨噬细胞是 CD45+F4/80+CD11b+Gr1- 并表达巨噬细胞特异性 Csf1r-GFP 报告基因。在趋化因子受体缺陷 (Cx3cr1-/-) 胚胎的 HBA 中，红细胞生成的减少伴随着 HBA 巨噬细胞百分比的减少。在共培养中，我们发现头部巨噬细胞将 HBA 内皮细胞的 HPC 数量提高了 2 倍以上，并且促炎因子 TNFα 由头部巨噬细胞产生并影响体外 HBA 造血。总之，头部巨噬细胞在 HBA 红细胞生成和 HS/PC 扩增和/或成熟中发挥积极作用，在造血发育中充当微环境细胞调节剂。并且促炎因子 TNFα 由头部巨噬细胞产生并影响体外 HBA 造血。总之，头部巨噬细胞在 HBA 红细胞生成和 HS/PC 扩增和/或成熟中发挥积极作用，在造血发育中充当微环境细胞调节剂。并且促炎因子 TNFα 由头部巨噬细胞产生并影响体外 HBA 造血。总之，头部巨噬细胞在 HBA 红细胞生成和 HS/PC 扩增和/或成熟中发挥积极作用，在造血发育中充当微环境细胞调节剂。