Single-cell transcriptomic atlas reveals increased regeneration in diseased human inner ear balance organs.

Mammalian inner ear hair cell loss leads to permanent hearing and balance dysfunction. In contrast to the cochlea, vestibular hair cells of the murine utricle have some regenerative capacity. Whether human utricular hair cells regenerate in vivo remains unknown. Here we procured live, mature utricles from organ donors (9 ears from 6 organ donors) and vestibular schwannoma patients (24 ears from 24 patients), and presented a single-cell transcriptomic atlas at unprecedented resolution. We validated marker genes using immunostaining and RNAscope in situ hybridization and described previously unknown markers of 13 sensory and non-sensory cell types. In addition, we compared and found partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncovered transcriptomes unique to hair cell precursors, which are validated in both organ donor and vestibular schwannoma utricles. Unexpectedly we found 14-fold more hair cell precursors in vestibular schwannoma utricles, demonstrating the existence of ongoing regeneration in humans. Lastly, supporting cell-to-hair cell trajectory analysis revealed 5 distinct patterns of dynamic gene expression and associated pathways. Our data-set constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear. [ABSTRACT FROM AUTHOR]