Agarwal, R.; Benjaminsen, J.; Lust, K.; Becker, C.; Fuchs, N.; Hasel de Carvalho, E.; Eggeler, F.; El Said Ibrahim, O.; Aghaallaei, N.; Bajoghli, B.; Wittbrodt, J.

Stem cell populations in tissues require precise regulation of their number and quality to maintain proper organ growth and regenerative capacity. Amongst various regulatory mechanisms, immune cells are emerging to directly regulate stem cell populations. The medaka retinal stem cell niche, a model for lifelong neurogenic growth, provides a system to study immune cell-stem cell interactions. Here we investigate how microglia, the resident macrophages of the central nervous system, regulate the retinal stem cell niche. We identify that bona fide retinal stem cells express the chemokine ccl25b while its cognate receptor, ccr9a, is expressed in microglia. These microglia form a static surveillance ring adjacent to the stem cell niche and actively phagocytose retinal stem cells. We show that targeted mutation of ccl25b affects microglia mobility and leads to reduction of retinal-stem cell-derived material in microglia. Interference with microglia by deletion of spi1b reveals that microglia absence leads to increased numbers of ccl25b-positive stem cells and results in morphological defects in the retinal stem cell niche and retina. Overall, our data show that under homeostatic conditions the retinal stem cell population, essential for proper eye development, is actively pruned by immune surveillance.