A comparative single-cell transcriptomic atlas for diverse populations of vertebrate hair cells
Year: 2026
Type: preprint
Abstract: Mechanosensitive hair cells vary widely in morphology and regenerative capacity across vertebrate organs and species. To investigate their underlying transcriptomic diversity, we integrated human, mouse, chicken, and zebrafish single-cell and single-nucleus RNA sequencing datasets and assembled a cross-species atlas of hair cells spanning organs, developmental stages, and species. Analysis of 29 hair cell populations, encompassing the major cochlear, vestibular, and lateral-line hair cell types, identified approximately 5,000 genes enriched in at least one hair cell population compared to supporting cells from the same organs. Unsupervised clustering of these hair cell-enriched (HCE) genes defined species-, organ-, and hair cell state–associated cohorts as well as broadly conserved hair cell-enriched programs. Using an AUC-based scoring framework, we further defined 884 pan hair cell-enriched (pan-HCE) genes with elevated expression in most developing and/or mature hair cell populations, including genes implicated in deafness, mechanotransduction, and synaptic transmission, along with genes not previously linked to hair cell function. Independent analysis of developing hair cells using the same metrics stratified pan-HCE genes based on when they are first enriched and identified an additional 97 genes that are transiently enriched. We used the pan- and developing HCE gene sets to assess transcriptional similarity between baseline hair cell states and hair cells produced during avian hair cell regeneration and in mouse cochlear organoids, as well as hair cell-like populations produced by fibroblast reprogramming. HCE gene sets with different developmental dynamics identified young vs. more mature hair cells when projected onto independent single-cell RNA sequencing datasets from developing zebrafish, mouse, and human. We provide a web-based resource of all HCE metrics and expression profiles, enabling future exploration of vertebrate hair cell gene expression across organs, species, and experimental contexts.
Authors: Mahashweta Basu, Nesrine Benkafadar, Beatrice Milon, Carlo Colantuoni, Brian R. Herb, Amanda Ciani Berlingeri, Ivan A. Cruz, Joshua Orvis, Emilia Luca, Mitsuo P. Sato, Dunia Abdul-Aziz, Meghan Dewan, Kathleen Gwilliam, Gabriella Manilla, Christopher Shults, R. Shaun Adkins, Yang Song, Anup Mahurkar, John V. Brigande, Alain Dabdoub, Albert Edge, Andrew K. Groves, Ksenia Gnedeva, Stefan Heller, Ronna Hertzano, Tatjana Piotrowski, David W. Raible, Yehoash Raphael, Jennifer Stone, Litao Tao, Mark E. Warchol, Seth A. Ament, Lisa V. Goodrich
Institutions: University of Maryland, Baltimore, Inserm, Université de Montpellier, Institute for Neurosciences of Montpellier, Stanford Medicine, Institute for Stem Cell Biology and Regenerative Medicine, Stanford University, National Institutes of Health, National Institute on Deafness and Other Communication Disorders, University of Washington, Sunnybrook Research Institute, Massachusetts Eye and Ear Infirmary, Harvard University, Oregon Health & Science University, University of Toronto, Washington University in St. Louis, University of Southern California, Stowers Institute for Medical Research, University of Michigan, Michigan Medicine, Creighton University
Language: English
Subfield: Sensory Systems
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: Dissecting the sensory hair cell nucleus: Development of a novel method for investigating chromatin interactions (Tn5-Capture) in small cell numbers, G4659374921, G5175560452, G5665195824, Zebrafish Sensory Hair Cell Regeneration, G9000010485, G9000146556, G9000239593, G9000255464, Avian-inspired Regenerative Therapies for Hearing Loss, Hippo-mediated control of growth and regeneration in the inner ear sensory organs, Regenerative pathways in the avian cochlea, Macrophage Response to Otic Pathology, The gEAR portal - Advancing Data Sharing, Analysis and Discovery for Hearing and Balance Research, Enhancing Atoh1 function in hair cell regeneration, Determination of Hair Cell Fate from Postnatal Cochlear Supporting Cells
OpenAlex ID: W7212280499