Stem cell aging and plasticity in the Drosophila nervous system

The majority of neural stem cells (NSCs) are considered as very plastic precursors that, in vitro, can divide indefinitely or differentiate into neurons or glia under specific conditions. However, in vivo, these cells actively proliferate during development, and later enter quiescence or apoptosis. This raises the issue as to whether stem cells keep their plastic behavior throughout their life, which may impact their therapeutic potential in regenerative medicine. Using the Gcm/Glide (for Glial cell missing/Glial cell deficient) transcription factor, which is able to trigger a complete and stable fate conversion into glia when ectopically expressed, we recently reported that the plasticity of Drosophila NSCs, commonly called neuroblasts (NBs), is age-dependent. When challenged with Gcm/Glide, newborn NBs are more easily converted into glia than old ones. Furthermore, the few old NBs that can be converted frequently generate cells with a stable (NB/glia) intermediate identity, a phenotype characteristic of cancer cells. We here discuss the concept of aging in NSC fate conversion and speculate on how our findings impact the ongoing debate concerning NSC plasticity.