Transparent Adult Zebrafish as a Tool for In Vivo Transplantation Analysis

Richard Mark White,1,2,3 Anna Sessa,2 Christopher Burke,2 Teresa Bowman,2 Jocelyn LeBlanc,2 Craig Ceol,2 Caitlin Bourque,2 Michael Dovey,2,3 Wolfram Goessling,2,3 Caroline Erter Burns,4 and Leonard I. Zon1,2,3,

1 Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA
2 Division of Hematology/Oncology, Children's Hospital Boston, Boston, MA 02115, USA
3 Harvard Medical School, Boston, MA 02115, USA
4 Massachusetts General Hospital, Boston, MA 02114, USA

Corresponding author
Leonard I. Zon
zon@enders.tch.harvard.edu

The zebrafish is a useful model for understanding normal and cancer stem cells, but analysis has been limited to embryogenesis due to the opacity of the adult fish. To address this, we have created a transparent adult zebrafish in which we transplanted either hematopoietic stem/progenitor cells or tumor cells. In a hematopoiesis radiation recovery assay, transplantation of GFP-labeled marrow cells allowed for striking in vivo visual assessment of engraftment from 2 hr–5 weeks posttransplant. Using FACS analysis, both transparent and wild-type fish had equal engraftment, but this could only be visualized in the transparent recipient. In a tumor engraftment model, transplantation of RAS-melanoma cells allowed for visualization of tumor engraftment, proliferation, and distant metastases in as little as 5 days, which is not seen in wild-type recipients until 3 to 4 weeks. This transparent adult zebrafish serves as the ideal combination of both sensitivity and resolution for in vivo stem cell analyses.

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