Insights into the molecular mechanisms regulating mammalian hair cell regeneration

Purpose of review To give an overview of recent advances in mammalian auditory hair cell regeneration. Recent findings Supporting cells act as progenitors to regenerate hair cells in the prehearing mammalian cochlea but not in the mature cochlea. To overcome this developmental obstacle, manipulation of multiple genes and intracellular pathways has been investigated, which has obtained promising data. This review focuses on recent advances in auditory hair cell regeneration, including synergic gene regulation associated with Atoh1 and Notch signaling, epigenetics, and functional recovery of regenerated hair cells. Co-manipulation of genes critical for hair cell development and cell cycle re-entry, including Atoh1, Isl1, Pou4f3, Gata3, Gfi1, P27(kip1), RB, Myc, and Notch-signaling genes, has generated hair cell-like cells in the adult cochlea both in vitro and in vivo. The epigenetic mechanism has been studied in hair cell development and regeneration. Regeneration of hair cell function has a very limited progress, which lacks in-vitro and in-vivo electrophysiology data. Regeneration of adult auditory hair cells remains a major challenge. Manipulation of multiple genes and pathways together with epigenetic regulation might potentially regenerate functional hair cells in the adult mammalian cochlea.