Cochlear transcriptome analysis of an outbred mouse population (CFW).

Autor:	Boussaty EC; Department of Otolaryngology, University of California, San Diego, La Jolla, CA, United States., Tedeschi N; J. Craig Venter Institute, La Jolla, CA, United States., Novotny M; J. Craig Venter Institute, La Jolla, CA, United States., Ninoyu Y; Department of Otolaryngology, University of California, San Diego, La Jolla, CA, United States., Du E; Department of Otolaryngology, University of California, San Diego, La Jolla, CA, United States., Draf C; Department of Otolaryngology, University of California, San Diego, La Jolla, CA, United States., Zhang Y; J. Craig Venter Institute, La Jolla, CA, United States., Manor U; Department of Cell and Developmental Biology, University of California San Diego, Salk Institute for Biological Studies, Waitt Advanced Biophotonics Center, La Jolla, CA, United States., Scheuermann RH; J. Craig Venter Institute, La Jolla, CA, United States.; Department of Pathology, University of California, San Diego, La Jolla, CA, United States., Friedman R; Department of Otolaryngology, University of California, San Diego, La Jolla, CA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in cellular neuroscience [Front Cell Neurosci] 2023 Nov 29; Vol. 17, pp. 1256619. Date of Electronic Publication: 2023 Nov 29 (Print Publication: 2023).
DOI:	10.3389/fncel.2023.1256619
Abstrakt:	Age-related hearing loss (ARHL) is the most common cause of hearing loss and one of the most prevalent conditions affecting the elderly worldwide. Despite evidence from our lab and others about its polygenic nature, little is known about the specific genes, cell types, and pathways involved in ARHL, impeding the development of therapeutic interventions. In this manuscript, we describe, for the first time, the complete cell-type specific transcriptome of the aging mouse cochlea using snRNA-seq in an outbred mouse model in relation to auditory threshold variation. Cochlear cell types were identified using unsupervised clustering and annotated via a three-tiered approach-first by linking to expression of known marker genes, then using the NSForest algorithm to select minimum cluster-specific marker genes and reduce dimensional feature space for statistical comparison of our clusters with existing publicly-available data sets on the gEAR website, and finally, by validating and refining the annotations using Multiplexed Error Robust Fluorescence In Situ Hybridization (MERFISH) and the cluster-specific marker genes as probes. We report on 60 unique cell-types expanding the number of defined cochlear cell types by more than two times. Importantly, we show significant specific cell type increases and decreases associated with loss of hearing acuity implicating specific subsets of hair cell subtypes, ganglion cell subtypes, and cell subtypes within the stria vascularis in this model of ARHL. These results provide a view into the cellular and molecular mechanisms responsible for age-related hearing loss and pathways for therapeutic targeting. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Boussaty, Tedeschi, Novotny, Ninoyu, Du, Draf, Zhang, Manor, Scheuermann and Friedman.)
Databáze:	MEDLINE
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