title: Characterization of immune-matched hematopoietic transplantation in zebrafish.
abstract: 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 multilineage engraftment at 3 months after transplantation. 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 percentage donor chimerism compared with 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.
authors.affiliation: Stem Cell Program and Division of Hematology/Oncology Children's Hospital Boston and Dana-Farber Cancer Institute, Howard Hughes Medical Institute, Harvard Stem Cell Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Jill L O
authors.initials: JL
authors.lastname: de Jong
authors.forename: Caroline Erter
authors.initials: CE
authors.lastname: Burns
authors.forename: Aye T
authors.initials: AT
authors.lastname: Chen
authors.forename: Emily
authors.initials: E
authors.lastname: Pugach
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Mayhall
authors.forename: Alexandra C H
authors.initials: AC
authors.lastname: Smith
authors.forename: Henry A
authors.initials: HA
authors.lastname: Feldman
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhou
authors.forename: Leonard I
authors.initials: LI
authors.lastname: Zon
mesh_terms: D000818:Animals; D046528:Chimerism; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D008285:Major Histocompatibility Complex; D023421:Models, Animal; D019172:Transplantation Conditioning / Q000379:methods; D015027:Zebrafish / Q000276:immunology* / Q000601:surgery*