During development, hematopoietic stem cells (HSCs) are produced from the hemogenic endothelium and will expand in a transient hematopoietic niche. Prostaglandin E₂ (PGE2) is essential during vertebrate development and HSC specification, but its precise source in the embryo remains elusive. Here, we show that in the zebrafish embryo, PGE2 synthesis genes are expressed by distinct stromal cell populations, myeloid (neutrophils, macrophages), and endothelial cells of the caudal hematopoietic tissue. Ablation of myeloid cells, which produce the PGE2 precursor prostaglandin H₂ (PGH2), results in loss of HSCs in the caudal hematopoietic tissue, which could be rescued by exogeneous PGE2 or PGH2 supplementation. Endothelial cells contribute by expressing the PGH2 import transporter slco2b1 and ptges3, the enzyme converting PGH2 into PGE2. Of note, differential niche cell expression of PGE2 biosynthesis enzymes is also observed in the mouse fetal liver. Taken altogether, our data suggest that the triad composed of neutrophils, macrophages, and endothelial cells sequentially and synergistically contributes to blood stem cell expansion during vertebrate development.

中文翻译：

---

骨髓和内皮细胞协同合成前列腺素 E 促进脊椎动物胎儿造血干细胞扩增

在发育过程中，造血干细胞 (HSC) 由造血内皮产生，并将在短暂的造血生态位中扩增。前列腺素 E ₂ (PGE2) 在脊椎动物发育和 HSC 规范过程中是必不可少的，但其在胚胎中的确切来源仍然难以捉摸。在这里，我们表明在斑马鱼胚胎中，PGE2 合成基因由不同的基质细胞群、骨髓（中性粒细胞、巨噬细胞）和尾部造血组织的内皮细胞表达。产生 PGE2 前体前列腺素 H ₂ (PGH2) 的骨髓细胞的消融导致尾部造血组织中 HSC 的损失，这可以通过外源性 PGE2 或 PGH2 补充来挽救。内皮细胞通过表达 PGH2 输入转运蛋白做出贡献slco2b1和ptges3，将 PGH2 转化为 PGE2 的酶。值得注意的是，在小鼠胎肝中也观察到 PGE2 生物合成酶的差异生态位细胞表达。总而言之，我们的数据表明，由中性粒细胞、巨噬细胞和内皮细胞组成的三联体依次协同地促进了脊椎动物发育过程中的造血干细胞扩增。