title: A Functional Bioluminescent Zebrafish Screen for Enhancing Hematopoietic Cell Homing.
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 E2on 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.
authors.affiliation: Department of Pediatrics, Blood and Marrow Transplant Program, University of Minnesota Medical School, MMC 366, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA.
authors.forename: Yuliana
authors.initials: Y
authors.lastname: Astuti
authors.affiliation: Department of Pediatrics, Blood and Marrow Transplant Program, University of Minnesota Medical School, MMC 366, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA.
authors.forename: Ashley C
authors.initials: AC
authors.lastname: Kramer
authors.affiliation: Department of Pediatrics, Blood and Marrow Transplant Program, University of Minnesota Medical School, MMC 366, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Blake
authors.affiliation: Department of Pediatrics, Blood and Marrow Transplant Program, University of Minnesota Medical School, MMC 366, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA.
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Blazar
authors.affiliation: Department of Pediatrics, Blood and Marrow Transplant Program, University of Minnesota Medical School, MMC 366, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA.
authors.forename: Jakub
authors.initials: J
authors.lastname: Tolar
authors.affiliation: Department of Pediatrics, Blood and Marrow Transplant Program, University of Minnesota Medical School, MMC 366, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA.
authors.forename: Mandy E
authors.initials: ME
authors.lastname: Taisto
authors.affiliation: Department of Pediatrics, Blood and Marrow Transplant Program, University of Minnesota Medical School, MMC 366, 420 Delaware Street Southeast, Minneapolis, MN 55455, USA. Electronic address: lundx072@umn.edu.
authors.forename: Troy C
authors.initials: TC
authors.lastname: Lund
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000502:physiology; D002465:Cell Movement; D002470:Cell Survival; D058948:Cell Tracking / Q000379:methods; D004875:Ergosterol / Q000494:pharmacology; D015870:Gene Expression; D017930:Genes, Reporter; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D008163:Luminescent Measurements / Q000379:methods; D019718:Receptors, CXCR4 / Q000378:metabolism; D014019:Tissue Donors; D015027:Zebrafish
chemical_list: D019718:Receptors, CXCR4; D004875:Ergosterol
keywords: bioluminescent; ergosterol; homing; vitamin D; zebrafish