Hierarchical stem cell topography splits growth and homeostatic functions in the fish gill

While lower vertebrates contain adult stem cells (aSCs) that maintain homeostasis and drive in-exhaustive organismal growth, mammalian aSCs display mainly the homeostatic function. Understanding aSC-driven growth is of paramount importance to promote organ regeneration and prevent tumour formation in mammals. Here we present a clonal approach to address common or dedicated populations of aSCs for homeostasis and growth. Our functional assays on medaka gills demonstrate the existence of separate homeostatic and growth aSCs, which are clonal but differ in their topology. While homeostatic aSCs are fixed, embedded in the tissue, growth aSCs locate at the expanding peripheral zone. Modifications in tissue architecture can convert the homeostatic zone into a growth zone, indicating a leading role for the physical niche defining stem cell output. We hypothesise that physical niches are main players to restrict aScs to a homeostatic function in animals with a fixed adult size.