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

Abstract

During development, hematopoietic stem cells (HSCs) are produced from the hemogenic endothelium and will expand in a transient hematopoietic niche. Prostaglandin E 2 (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 2 (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.

Altered Morpho-Functional Features of Neurogenesis in Zebrafish Embryos Exposed to Non-Combustion-Derived Magnetite

“…All efforts were made to comply to the 3R guidelines. Embryos were obtained as described previously [ 49 , 50 ]. Zebrafish embryos were treated from 4 h post-fertilization (hpf) up to 96 hpf with different magnetite concentrations (100; 200; 400; 600; 800 µg/mL) to define the survival rate and morphology defects.…”

Minichromosome maintenance protein 10 (mcm10) regulates hematopoietic stem cell emergence in the zebrafish embryo

“…cmyb, runx1, pu.1, mfap4, mpx, gata1, gata2b, flk1, and rag1 antisense probes (digoxigenin and fluorescein labeled) were previously described and used in our laboratory ( Cacialli et al., 2021 , 2022 ; Mahony et al., 2021 ). WISH was performed on 4% paraformaldehyde-fixed embryos.…”

Exposure of Zebrafish Embryos to Urea Affects NOS1 Gene Expression in Neuronal Cells

“…Embryos were obtained as described previously [36,37], were dechorionized, and then, treated from 4 to 96 h post-fertilization (hpf) with different urea concentrations (0, 10, 50, 100 mM) dissolved in E3 zebrafish medium (34.8 g of NaCl, 1.6 g of KCl, 5.8 g of CaCl 2 , 2H 2 O, 9.78 g of MgCl 2 , 6H 2 O) in standard housing conditions to define the survival rate and morphology defects. Urea concentrations were chosen based on our previous studies [21].…”