Figure 1. dmPGE₂ regulates vertebrate HSC function.

(A) A schematic representation depicts the basic workflow for the zebrafish chemical screen that identified dmPGE₂ and an endogenous role for prostaglandin signaling in HSC formation. Adult zebrafish were in-crossed and collected embryos were treated with chemicals from the 3-somite stage to 36 hours post fertilization. Whole embryo in situ hybridization to runx1/cmyb (conserved HSC markers) was then used to examine HSC formation. Embryos treated with the stable derivative dmPGE₂ displayed increased runx1/cmyb staining in the AGM whereas treatment with the Cox inhibitor indomethacin led to reduced HSC formation. (B) 2-hour ex vivo pulse treatment with dmPGE₂ leads to increases in HSC function that last for as long as five serial transplantations. (C) Prolonged in vivo exposure to dmPGE₂ leads to enhanced engraftment; however, the treated cells eventually exhaust and lose differentiation potential. (D) dmPGE₂ signals through EP2 and EP4 receptors and an interaction with Wnt signaling. Downstream transcriptional changes lead to improved homing, survival and proliferation of the HSCs.