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Understanding mechanisms of stem cell regulation is crucial for regenerative medicine as well as for new therapies for developmental defects and cancer. Using Xenopus laevis neural crest, an embryonic stem cell population, as a model system, Blackiston et al. show that modulating the bioelectrical state of a population of ‘instructor’ cells expressing the native glycine receptor chloride channel can trigger a neoplastic phenotype in other cells, an effect that is mediated by long-range serotonergic signalling. Modulating membrane voltage is therefore a potentially powerful therapeutic approach for manipulating stem cells.