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- Title
Mapping human inner ear development: insights from single-nucleus transcriptomics.
- Authors
van der Valk, W. H.; van Beelen, E. S. A.; Udayappan, S. D.; de Groot, J. C. M. J.; Koehler, K. R.; van Benthem, P. P. G.; Locher, H.
- Abstract
The inner ear, essential for auditory perception and balance, relies on specialized cell types whose developmental mechanisms are incompletely understood. While animal models provide valuable insights, human inner ear development remains predominantly characterized by descriptive approaches. The advent of single-cell transcriptomics offers a promising approach to decode the complexities of human inner ear development. In this study, we introduce the Human Inner Ear Developmental snRNAseq Atlas (HIEDRA), a comprehensive single-nucleus RNA transcriptomic dataset that covers the entire membranous human inner ear at nine developmental stages from fetal weeks 7 to 15. Our analysis of over 55,000 cells reveals the molecular dynamics that drive the differentiation of epithelial, neuronal, and mesenchymal cell populations in both vestibular and cochlear regions. We provide new insights into specific gene markers that differentiate cochlear from vestibular cell types. We additionally find the involvement of canonical signaling pathways such as Notch, Wnt, and Hippo in sensory cell type development - a correlation previously established in non-human models. Moreover, our data reveal the contribution of additional signaling pathways, including TNF, to hair cell formation in silico. We also identify the role of ErbB, Notch and Hippo signaling pathways in the specification of key nonsensory epithelial cell types: vestibular dark cells and cochlear marginal cells, which are crucial for inner ear function. Our findings not only clarify the complex landscape of human inner ear development but also highlight the diverse roles of otic mesenchymal cells, previously underappreciated in this context. This characterization deepens our understanding of human inner ear development and offers potential to explore pathophysiological mechanisms that lead to hearing loss and balance disorders. Furthermore, leveraging these insights to improve culture models, such as human pluripotent stem cell-derived inner ear organoids, could significantly boost their applicability for in vitro studies of developmental processes and their efficacy as disease models.
- Subjects
POLAND; TISSUES; CONFERENCES &; conventions; CELL culture; INNER ear; GENE expression profiling; CELL differentiation; HAIR cells
- Publication
Journal of Hearing Science, 2024, Vol 14, Issue 3, p111
- ISSN
2083-389X
- Publication type
Article