To discover small molecules that modulate hematopoietic cell homing after adoptive transfer, we created a transgenic zebrafish expressing firefly luciferase downstream of the ubiquitin promoter (ubi:luc) to serve as a hematopoietic donor. Bioluminescence imaging (BLI) was used to detect and follow ubi:luc hematopoietic cells that homed to the marrow as early as 1 day post-transplant. BLI was able to detect the biological effect of prostaglandin E2 on early homing/engraftment of donor hematopoietic cells. This system was utilized in a functional screen of small molecules to enhance homing/engraftment. We discovered a phytosterol, ergosterol, that could increase hematopoietic cell homing in zebrafish and mice. In addition, ergosterol increased CXCR4 expression and promoted expansion of Lin−SCA-1+KIT+ cells in vitro. We have demonstrated the utility of in vivo BLI to non-invasively monitor donor hematopoietic cell activity in adult zebrafish as a functional screen for mediators of cellular homing.
Bibliographical noteFunding Information:
We gratefully thank the laboratory of Dr. Zon for sharing the ubiquitin promoter fragment. Research reported in this publication was supported by the National Heart, Lung and Blood Institute of the NIH under award number K08HL108998 (T.C.L.), ASH Junior Faculty Scholar Award (T.C.L.), the University of Minnesota Children's Discovery Fund (T.C.L.), a University of Minnesota Academic Health Center Seed Grant (T.C.L.), and a Minnesota Regenerative Medicine Grant (T.C.L.).
© 2017 The Author(s)
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