The Field of Hair Cell Regeneration Is Ready for Input from Genomics and Epigenetics

Cochlear hair cells are epithelial cells that are not replaced when lost, leading to permanent hearing loss. The lack of spontaneous regeneration of hair cells is a rarity in epithelial tissues, including hair cell epithelia. Evolutionary considerations may explain why hair cell regenerative capacity of mammals was lost during the evolution of the cochlea. In parallel, at the molecular level, studies using transgenesis and developmental biology have revealed some of the key signaling molecular players that govern the development of hair cells and their neighboring supporting cells and provided candidates for manipulating the system to induce regeneration. Gene transfer technology using viruses showed proof of principle for the ability to induce the transdifferentiation of supporting cells to new hair cells, but the outcome is inconsistent and of low quantity and poor quality. Further use of modern sequencing technology should reveal additional details of gene expression and its regulation in the process of regenerating hair cell organs such as in fish, birds, and mammalian balance organs. Sequence data generated from supporting cells in mature ears with hair cell lesions, at the level of gene expression and its epigenetic regulation, will assist in designing these therapeutic interventions. Still, rebuilding a perfect new cochlea to provide normal hearing in profoundly deaf ears remains a formidable challenge.