Single-cell Transcriptomic Atlas Reveals Increased Regeneration in Diseased Human Inner Ear Balance Organs

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Jun 6

PMID 38844821

Authors

Tian Wang

Angela H Ling

Sara E Billings

Davood K Hosseini

Yona Vaisbuch

Grace S Kim

Patrick J Atkinson

Zahra N Sayyid

Ksenia A Aaron

Dhananjay Wagh

Nicole Pham

Mirko Scheibinger

Ruiqi Zhou

Akira Ishiyama

Lindsay S Moore

Peter Santa Maria

Nikolas H Blevins

Robert K Jackler

Jennifer C Alyono

John Kveton

Dhasakumar Navaratnam

Stefan Heller

Ivan A Lopez

Nicolas Grillet

Taha A Jan

Alan G Cheng

Affiliations

Soon will be listed here.

Abstract

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.

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