daf-18/PTEN locally antagonizes insulin signalling to couple germline stem cell proliferation to oocyte needs in C. elegans

Abstract

During development, stem cell populations rapidly proliferate to populate the expanding tissues and organs. During this phase, nutrient status, through systemically affecting insulin/IGF-1 signalling, largely dictates stem cell proliferation rates. In adults however, differentiated stem cell progeny requirements are generally reduced and vary according to the spatio-temporal needs of each tissue. We demonstrate here that differential regulation of germline stem cell proliferation rates in C. elegans adults is accomplished through localized neutralization of insulin/IGF-1 signalling, requiring daf-18/PTEN, but not daf-16/FOXO. Indeed, the specific accumulation of oocytes, the terminally-differentiated stem cell progeny, triggers a feedback signal that locally antagonizes insulin/IGF-1 signalling outputs in the germ line, regardless of their systemic levels, to block germline stem cell proliferation. Thus, during adulthood, stem cells can differentially respond within tissues to otherwise equal insulin/IGF-1 signalling inputs, according to the needs for production of their immediate terminally-differentiated progeny.