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
-
- Cell Movement*
- Bone Marrow Cells/physiology
- Luminescent Measurements*/methods
- Ergosterol/pharmacology
- Cell Tracking*/methods
- Genes, Reporter
- Gene Expression
- Hematopoietic Stem Cells/physiology*
- Tissue Donors
- Animals
- Hematopoietic Stem Cell Transplantation
- Cell Survival
- Zebrafish
- Receptors, CXCR4/metabolism
- PubMed
- 28041876 Full text @ Stem Cell Reports
Citation
Astuti, Y., Kramer, A.C., Blake, A.L., Blazar, B.R., Tolar, J., Taisto, M.E., Lund, T.C. (2017) A Functional Bioluminescent Zebrafish Screen for Enhancing Hematopoietic Cell Homing. Stem Cell Reports. 8(1):177-190.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping