PUBLICATION
A novel conditioning-free hematopoietic stem cell transplantation model in zebrafish
- Authors
- Fraint, E., Feliz Norberto, M., Bowman, T.V.
- ID
- ZDB-PUB-201223-5
- Date
- 2020
- Source
- Blood advances 4: 6189-6198 (Journal)
- Registered Authors
- Bowman, Teresa
- Keywords
- none
- MeSH Terms
-
- Animals
- Bone Marrow
- Bone Marrow Transplantation
- Hematopoietic Stem Cell Transplantation*
- Hematopoietic Stem Cells
- Mice
- Zebrafish*
- PubMed
- 33351115 Full text @ Blood Adv
Citation
Fraint, E., Feliz Norberto, M., Bowman, T.V. (2020) A novel conditioning-free hematopoietic stem cell transplantation model in zebrafish. Blood advances. 4:6189-6198.
Abstract
Transplantation is the most common assay for measuring the in vivo functionality of hematopoietic stem cells (HSCs). Although various HSC transplantation strategies have been developed in zebrafish, they are underutilized because of challenges related to immune matching and preconditioning toxicity. To circumvent these limitations, we developed a simple and robust transplantation model using HSC-deficient hosts. Homozygous runx1W84X mutants are devoid of definitive hematopoietic cells, including HSCs and adaptive immune cells; thus, they require no preconditioning regimen for transplantation. Marrow cell transplantation into runx1-mutant zebrafish 2 days after fertilization significantly improved their survival to adulthood and resulted in robust, multilineage, long-lasting, serially repopulating engraftment. Furthermore, we demonstrated that engraftment into runx1 homozygous mutants was significantly higher than into runx1 heterozygotes, demonstrating that the improved transplantation success is attributable to the empty HSC niche in mutants and not just the embryonic environment. Competitive transplantation of marrow cells into runx1 mutants revealed a stem cell frequency similar to that of murine marrow cells, which demonstrates the utility of this model for quantifying HSC function. The streamlined approach and robustness of this assay will help broaden its feasibility for future high-throughput transplantation experiments in zebrafish and will enable further novel discoveries in the biology of HSCs.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping