Exploring life-long tissue homeostasis through lineage tracing and cell transplantation

Here, we introduce the Killibow, an inducible transgenic model for in-vivo multicolor lineage tracing in the naturally short-lived turquoise killifish (N. furzeri). We demonstrate that Cre-mediated recombination in transgenic fish can generate robust and stochastic labeling that remains stable during aging and regeneration.

In addition, to achieve inducible control of recombination, we either utilize in-vivo Cre electroporation or use the tamoxifen system in Killibow-derived cells. To further enable transplantation assays, we establish the first immunocompromised killifish model by mutating rag2. RNA sequencing reveals that rag2 mutants exhibit severely compromised expression of V(D)J recombination products, including immunoglobulins.