Activation and inhibition of Notch signaling facilitate proliferative regeneration of sensory cells in adult mice

Abstract Due to the limited regenerative capacity in adult mammals, the loss of vestibular hair cells (HCs) leads to balance disorders. In this study, we chronologically reprogrammed adult vestibular supporting cells (SCs) via bimodal regulation of Notch signaling, mimicking dynamic changes in Notch signaling during inner ear development. We found that activating Notch signaling stimulated SC proliferation in damaged adult utricles, priming these cells with the potential to regenerate sensory HCs. Subsequent inhibition of Notch signaling removed lateral inhibition barriers, promoting the transition from proliferating SCs to HCs. Our findings underscore the crucial role of Notch signaling in promoting vestibular HC regeneration.