PUBLICATION

A Functional Bioluminescent Zebrafish Screen for Enhancing Hematopoietic Cell Homing

Authors
Astuti, Y., Kramer, A.C., Blake, A.L., Blazar, B.R., Tolar, J., Taisto, M.E., Lund, T.C.
ID
ZDB-PUB-170104-7
Date
2017
Source
Stem Cell Reports   8(1): 177-190 (Journal)
Registered Authors
Lund, Troy
Keywords
bioluminescent, ergosterol, homing, vitamin D, zebrafish
MeSH Terms
  • Animals
  • Bone Marrow Cells/physiology
  • Cell Movement*
  • Cell Survival
  • Cell Tracking*/methods
  • Ergosterol/pharmacology
  • Gene Expression
  • Genes, Reporter
  • Hematopoietic Stem Cell Transplantation
  • Hematopoietic Stem Cells/physiology*
  • Luminescent Measurements*/methods
  • Receptors, CXCR4/metabolism
  • Tissue Donors
  • Zebrafish
PubMed
28041876 Full text @ Stem Cell Reports
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 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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping