Journal Article

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

Cheng, Alan G., Ling, Angela H., Kveton, John, Kim, Grace S., Grillet, Nicolas, Vaisbuch, Yona, Sayyid, Zahra N., Ishiyama, Akira, Maria, Peter Santa, Alyono, Jennifer C., Lopez, Ivan A., Jackler, Robert K., Pham, Nicole, Wagh, Dhananjay, Aaron, Ksenia A., Billings, Sara E., Moore, Lindsay S., Wang, Tian, Navaratnam, Dhasakumar, Zhou, Ruiqi, Heller, Stefan, Jan, Taha A., Atkinson, Patrick J., Blevins, Nikolas H., Hosseini, Davood K., Scheibinger, Mirko

2024

Overview

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 and vestibular schwannoma patients, and present a validated single-cell transcriptomic atlas at unprecedented resolution. We describe markers of 13 sensory and non-sensory cell types, with partial overlap and correlation between transcriptomes of human and mouse hair cells and supporting cells. We further uncover transcriptomes unique to hair cell precursors, which are unexpectedly 14-fold more abundant 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, including Wnt and IGF-1 signaling. Our dataset constitutes a foundational resource, accessible via a web-based interface, serving to advance knowledge of the normal and diseased human inner ear. Loss of inner ear hair cells leads to permanent hearing loss and balance dysfunction. Whether human utricular cells regenerate is unknown. Here, the authors present a single-cell resource of utricular cells from organ donors and schwannoma patients and describe transcriptional changes during homeostasis and in response to damage.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/32 / 38/91 / 631/378/87 / 631/80/304 / 64 / 692/4017 / Animals / Balance / Balance organs / Cochlea / Ear / Ear, Inner - cytology / Ear, Inner - metabolism / Female / Gene expression / Gene Expression Profiling / Hair / Hair cells / Hair Cells, Vestibular - metabolism / Hearing / Hearing loss / Hearing protection / Homeostasis / Humanities and Social Sciences / Humans / Inner ear / Insulin-like growth factor I / Insulin-Like Growth Factor I - genetics / Insulin-Like Growth Factor I - metabolism / Insulin-like growth factors / Male / Mice / multidisciplinary / Neuroma, Acoustic - genetics / Neuroma, Acoustic - metabolism / Neuroma, Acoustic - pathology / Organ donors / Regeneration / Regeneration - genetics / Saccule and Utricle - cytology / Saccule and Utricle - metabolism / Schwann cells / Science / Science (multidisciplinary) / Single-Cell Analysis / Trajectory analysis / Transcriptome / Transcriptomes / Transcriptomics / Utricle / Vestibular system / Wnt protein