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Revealing heterogeneity and damage response in the adult human utricle [scRNA-Seq]

ABSTRACT: The human utricle is a vestibular organ composed of sensory and non-sensory cells responsible for maintaining balance. Balance sense gradually deteriorates with age. With the aging population expected to double to 2 billion by 2050, vestibular disorders will pose a significant challenge as no pharmaceutical or biological treatments are available, a current unmet medical need. Here we show, for the first time, the cellular and transcriptional profile of the adult human utricle and its response to damage by performing bulk and single-cell RNA-sequencing from patient-derived utricles. We discovered six transcriptionally distinct cell types, including a unique population, demonstrating the heterogeneity and complexity of the adult human utricle. In addition, using an aminoglycoside damage paradigm, we determined the early transcriptional changes of the utricle after damage. Our findings demonstrate that this organ has the capacity to respond to ototoxic damage within 24 h and potentially initiate a regenerative response via an early-responding supporting cell population. This study represents a major step forward in inner ear regenerative medicine. Our results will serve as a foundation for preclinical studies, paving the way to therapeutic strategies for balance recovery.

ORGANISM(S): Homo sapiens

PROVIDER: GSE244055 | GEO | 2025/10/13

REPOSITORIES: GEO

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Revealing heterogeneity and damage response in the adult human utricle

Project description:The human utricle is a vestibular organ composed of sensory and non-sensory cells responsible for maintaining balance. Balance sense gradually deteriorates with age. With the aging population expected to double to 2 billion by 2050, vestibular disorders will pose a significant challenge as no pharmaceutical or biological treatments are available, a current unmet medical need. Here we show, for the first time, the cellular and transcriptional profile of the adult human utricle and its response to damage by performing bulk and single-cell RNA-sequencing from patient-derived utricles. We discovered six transcriptionally distinct cell types, including a unique population, demonstrating the heterogeneity and complexity of the adult human utricle. In addition, using an aminoglycoside damage paradigm, we determined the early transcriptional changes of the utricle after damage. Our findings demonstrate that this organ has the capacity to respond to ototoxic damage within 24 h and potentially initiate a regenerative response via an early-responding supporting cell population. This study represents a major step forward in inner ear regenerative medicine. Our results will serve as a foundation for preclinical studies, paving the way to therapeutic strategies for balance recovery.

2025-10-13 | GSE242833 | GEO

Effect of subchronic ototoxic (3,3'-iminodipropionitrile - IDPN) exposure on the vestibular epithelium of the mouse

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Cell-type identity of the avian utricle

Project description:The avian utricle, a vestibular organ of the inner ear, displays turnover of sensory hair cells throughout life. This is in sharp contrast to the mammalian utricle, which shows limited regenerative capacity. Here, we use single-cell RNA-sequencing to identify distinct marker genes for the different sensory hair cell subtypes of the chicken utricle, which we validated in situ . We provide markers for spatially distinct supporting cell populations, and identified two transitional cell populations of dedifferentiating supporting cells and developing hair cells. Trajectory reconstruction resulted in an inventory of gene expression dynamics of natural hair cell generation in the avian utricle.

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Project description:The mammalian cochlea loses its ability to regenerate new hair cells prior to the onset of hearing. In contrast, the adult vestibular system can produce new hair cells in response to damage, or by reprogramming of supporting cells with the hair cell transcription factor Atoh1. We used RNA-seq and ATAC-seq to probe the transcriptional and epigenetic responses of utricle supporting cells to damage and Atoh1 transduction. We show that the improved regenerative response of the utricle correlates with a more accessible chromatin structure in utricle supporting cells compared to their cochlear counterparts. We also provide evidence that Atoh1 transduction of supporting cells is able to promote increased transcriptional accessibility of some hair cell genes. Our study offers a possible explanation for regenerative differences between sensory organs of the inner ear, but shows that additional factors to Atoh1 may be required for optimal reprogramming of hair cell fate.

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Dissociated avian utricle sensory epithelia treated with one of various siRNAs or small molecule inhibitors

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