A Functional Bioluminescent Zebrafish Screen for Enhancing Hematopoietic Cell Homing

Yuliana Astuti, Ashley C. Kramer, Amanda L. Blake, Bruce R Blazar, Jakub Tolar, Mandy E. Taisto, Troy C Lund

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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 LinSCA-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.

Original languageEnglish (US)
Pages (from-to)177-190
Number of pages14
JournalStem Cell Reports
Volume8
Issue number1
DOIs
StatePublished - Jan 10 2017

Keywords

  • bioluminescent
  • ergosterol
  • homing
  • vitamin D
  • zebrafish

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