As tissues age, the rate at which endogenous stem cells proliferate is known to decline, leading to prolonged periods of quiescence and fewer stem cell progeny. Nutrient status is a key regulator of stem cell proliferation; however, it remains fairly constant across all tissues in the body, whereas rates of stem cell proliferation can vary widely among tissues. In order to explain this phenomenon, there must be a mechanism for the local regulation of stem cell proliferation, but so far this has remained elusive. Now, on p. , Jean-Claude Labbé and colleagues uncover a process that mediates a local decline in germline stem cell (GSC) proliferation in C. elegans. The authors show that an accumulation of differentiated progeny, in this case oocytes, causes a decrease in GSC proliferation rates. Interestingly, this induced GSC quiescence is caused by local inhibition of insulin/IGF-1 signalling mediated by DAF-18/PTEN, but not DAF-16/FOXO, signalling downstream of oocyte accumulation. Since insulin/IGF-1 signalling operates in all animals including humans, these results represent an exciting breakthrough in our understanding of how stem cell proliferation and quiescence can be regulated in a tissue-specific manner, and may have important implications for disease.
