LIN28B/ let-7 control the ability of neonatal murine auditory supporting cells to generate hair cells through mTOR signaling

Significance Cochlear hair cell loss is a leading cause of deafness in humans and other mammals. In the immature cochlea, lost hair cells are regenerated by neighboring glia-like supporting cells. However, for reasons unknown, such regenerative capacity is rapidly lost as supporting cells undergo maturation. Here we identify a direct link between LIN28B, mammalian target of rapamycin (mTOR) activity, and supporting cell plasticity. Mimicking later developmental stages, we found that loss of the RNA binding protein LIN28B attenuated mTOR signaling and rendered young, immature supporting cells incapable of producing hair cells. Conversely, we found that reexpression of LIN28B reinstated the ability of maturing supporting cells to revert to a progenitor-like state and generate hair cells via activation of mTOR signaling.