Department of Pathology and Immunology, Faculty of Medicine, University of Geneva, Geneva 4, Switzerland.
Unité Lymphocytes et Immunité, Pasteur Institute, Paris Cedex 15, France.
EMBO J. 2022 Oct 4;41(19):e108536. doi: 10.15252/embj.2021108536. Epub 2022 Aug 4.
During development, hematopoietic stem cells (HSCs) are produced from the hemogenic endothelium and will expand in a transient hematopoietic niche. Prostaglandin E (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 H (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.
在发育过程中，造血干细胞（HSCs）由造血内皮细胞产生，并在短暂的造血龛位中扩增。前列腺素 E（PGE2）在脊椎动物发育和 HSC 特化过程中是必不可少的，但胚胎中其确切来源仍难以捉摸。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表达，包括髓样细胞（中性粒细胞、巨噬细胞）和尾造血组织的内皮细胞。髓样细胞（产生 PGE2 前体前列腺素 H（PGH2））的缺失导致尾造血组织中 HSCs 的丢失，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 摄取转运体 slco2b1 和 ptges3（将 PGH2 转化为 PGE2 的酶）做出贡献。值得注意的是，在小鼠胎肝中也观察到了不同龛位细胞表达 PGE2 生物合成酶。总的来说，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在脊椎动物发育过程中依次协同促进血液干细胞的扩增。
