A comparative single-cell transcriptomic atlas for diverse populations of vertebrate hair cells
- 1Harvard Medical School
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.
Related
- How small is too small? Genetic signatures from naturally small populations of a large island vertebrate, the Turks and Caicos Rock Iguana
- A Comparative Survey of Historical DNA Degradation From Vertebrate Museum Specimens: Unexpected Utility of Fluid-Preserved Specimens.
- Comparative Oogenesis in Annual and Non-annual African Killifishes: Oocyte Staging in the Fastest-Aging Vertebrate, Nothobranchius furzeri
- Novel genes and polymorphisms in human immunoglobulin light chains across diverse populations
- Are clinician-administered ataxia scales truly culture-free? Rethinking contextual validity in diverse populations
BibTeX
@misc{basu2026comparative,
title = {{A comparative single-cell transcriptomic atlas for diverse populations of vertebrate hair cells}},
author = {M. Basu and N. Benkafadar and B. Milon and C. Colantuoni and B. R. Herb and A. Ciani Berlinger and I. A. Cruz and J. Orvis and E. Luca and M. P. Sato and D. Abdul-Aziz and M. Dewan and K. Gwilliam and G. Manilla and C. Shults and R. S. Adkins and Y. Song and A. Markuhar and J. V. Brigande and A. Dabdoub and A. Edge and A. K. Groves and K. Gnedeva and S. Heller and R. Hertzano and T. Piotrowski and D. W. Raible and Y. Raphael and J. S. Stone and L. Tao and M. E. Warchol and S. Ament and L. V. Goodrich},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.02.748811},
url = {https://www.biorxiv.org/content/10.64898/2026.09.02.748811v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - A comparative single-cell transcriptomic atlas for diverse populations of vertebrate hair cells
AU - M. Basu
AU - N. Benkafadar
AU - B. Milon
AU - C. Colantuoni
AU - B. R. Herb
AU - A. Ciani Berlinger
AU - I. A. Cruz
AU - J. Orvis
AU - E. Luca
AU - M. P. Sato
AU - D. Abdul-Aziz
AU - M. Dewan
AU - K. Gwilliam
AU - G. Manilla
AU - C. Shults
AU - R. S. Adkins
AU - Y. Song
AU - A. Markuhar
AU - J. V. Brigande
AU - A. Dabdoub
AU - A. Edge
AU - A. K. Groves
AU - K. Gnedeva
AU - S. Heller
AU - R. Hertzano
AU - T. Piotrowski
AU - D. W. Raible
AU - Y. Raphael
AU - J. S. Stone
AU - L. Tao
AU - M. E. Warchol
AU - S. Ament
AU - L. V. Goodrich
PY - 2026
DA - 2026/09/02
PB - bioRxiv
DO - 10.64898/2026.09.02.748811
UR - https://www.biorxiv.org/content/10.64898/2026.09.02.748811v1
AB - 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.
ER -