Synergistic prostaglandin E synthesis by myeloid and endothelial cells promotes fetal hematopoietic stem cell expansion in vertebrates

SUMMARY

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. In this article published in EMBO Journal, GCIR member Julien Bertrand shows 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 exogenous 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, the data suggest that the triad composed of neutrophils, macrophages, and endothelial cells sequentially and synergistically contributes to blood stem cell expansion during vertebrate development.

This work has been funded by the Swiss National Fund.

•   Full article: https://doi.org/10.15252/embj.2021108536

Why is this article important?

Hematopoietic stem cells (HSCs) can regenerate all types of blood cells. The original pool of HSCs is established through many developmental processes that involve several specific microenvironments. A detailed understanding of the complex interactions between HSCs and their niche is therefore critical to improve HSC transplantation-based therapies. In this study, the research group led by GCIR member Julien Bertrand investigated the synthesis pathway of Prostaglandin E2 (PGE2). This molecule plays important roles during inflammation, it is the most abundant prostaglandin in the organism and it is known to enhance HSC expansion. Using embryonic zebrafish and mouse models, the authors show that all the genes involved in PGE2 synthesis are expressed by different cell types: neutrophils, macrophages, and endothelial cells are sequentially necessary to mediate PGE2 synthesis. Their results suggest that such a collaborative mechanism for PGE2 production and regulation of HSCs is likely conserved across vertebrates.

Picture in the box on the previous page by @ kazakovmaksim by Getty Images

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