Age and ER Stress Perturb a Neuronal Circuit Which Guards Germline Pluripotency and Fertility in C. elegans

How stem cells maintain pluripotency and avoid committing to a unique differentiated fate is a key problem in stem-cell biology with implications on many basic physiological processes including reproduction, development and aging. In this study, we used the model organism C. elegans to establish that neuronal cues regulate germline pluripotency in response to environmental and hormonal signals, coordinating between environmental conditions and the fate of the germline. Strikingly, this novel neuronal circuit is controlled by a single sensory neuron, which indirectly communicates with the gonad through serotonin, to actively repress precautious germline differentiation via epigenetic reprogramming. We further show that age and ER stress conditions perturb the integrity of this circuit, resulting in ectopic germline differentiation, and limiting the reproductive capacity of the organism.