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Cell transplantation into immunodeficient recipients is a widely-used approach to study stem cell and cancer biology; however, studying cell states post transplantation in vivo is inconvenient in mammals. Here, we generated a zebrafish foxn1/Casper mutant that is transparent and immunodeficient with deficient T cells. By employing the mutant for hematopoietic stem cell transplantation (HSCT), we could achieve nonconditioned transplantation. Meanwhile, we found that fetal HSCs from 3 days post fertilization produce a better transplant outcome in adult recipients, compared to adult HSCs. Furthermore, adult HSCs from the newly generated Tg (runx1:en-GFP) line have higher engraftment efficiency than that from the Tg (CD41:GFP) line. In addition to HSCT, foxn1/Casper mutant is feasible to allogeneic leukemia and muscle cell transplantation, as well as xenogenic medaka HSCT. Collectively, foxn1/Casper mutant permits the nonconditioned engraftment of multiple cell types with superiority in imaging and characterization of transplanted cells at single cell resolution in vivo.

The thymus is a central hematopoietic organ which produces mature T lymphocytes with diverse antigen specificity. During development, the thymus primordium is derived from the third pharyngeal endodermal pouch, and then differentiates into cortical and medullary thymic epithelial cells (TECs). TECs represent the primary functional cell type that forms the unique thymic epithelial microenvironment which is essential for intrathymic T-cell development, including positive selection, negative selection and emigration out of the thymus. Our understanding of thymopoiesis has been greatly advanced by using several important animal models. This review will describe progress on the molecular mechanisms involved in thymus and T cell development with particular focus on the signaling and transcription factors involved in this process in mouse and zebrafish.