The hair cells (HCs) of the inner ear mediate both our auditory and our vestibular senses. Following loss or damage, mammalian HCs show very limited capacity to regenerate, creating a therapeutic need to generate new HCs in vitro for cell replacement strategies. Domingos Henrique and co-workers now report a relatively simple and efficient protocol for deriving HCs from mouse embryonic stem cells, by expression of key transcription factors involved in HC differentiation during development (p. ). Co-expression of Atoh1 (traditionally considered the ‘master regulator’ of HC differentiation) with Gfi1 and Pou4f3 can efficiently induce a HC gene expression signature in embryoid body cells. Efficiency is further increased by either Notch pathway blockade or retinoic acid treatment. The resulting cells, termed induced HCs (iHCs) also show morphological and functional signs of HC differentiation: incipient stereociliary bundles and the presence of functional mechanotransduction channels. However, the iHCs are not fully mature, implying that additional extrinsic or intrinsic factors are required to direct terminal differentiation. Although this is not the first report of in vitro differentiation of HCs, the greater simplicity and efficiency of this protocol marks a significant step towards the goal of generating HCs in culture for research and therapeutic purposes.
