ZFIN ID: ZDB-PUB-110316-28
Characterization of immune-matched hematopoietic transplantation in zebrafish
de Jong, J.L., Burns, C.E., Chen, A.T., Pugach, E., Mayhall, E.A., Smith, A.C., Feldman, H.A., Zhou, Y., and Zon, L.I.
Evaluating hematopoietic stem cell (HSC) function in vivo requires a long-term transplantation assay. Although zebrafish are a powerful model for discovering the genetics of hematopoiesis, hematopoietic transplantation approaches have been underdeveloped. Here, we established a long-term reconstitution assay in adult zebrafish. Primary and secondary recipients showed multi-lineage engraftment at 3 months post-transplant. Limiting dilution data suggest that at least 1 in 65,000 zebrafish marrow cells contain repopulating activity, consistent with mammalian HSC frequencies. We defined zebrafish haplotypes at the proposed Major Histocompatibility Complex locus on chromosome 19 and tested functional significance through hematopoietic transplantation. Matching donors and recipients dramatically increased engraftment and percent donor chimerism compared to unmatched fish. These data constitute the first functional test of zebrafish histocompatibility genes, enabling the development of matched hematopoietic transplantations. This lays the foundation for competitive transplantation experiments with mutant zebrafish HSCs and chemicals to test for effects on engraftment, thereby providing a model for human hematopoietic diseases and treatments not previously available.