Cochlear transcriptome analysis of an outbred mouse population (CFW)
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,...
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fncel.2023.1256619/full |
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| author | Ely Cheikh Boussaty Neil Tedeschi Mark Novotny Yuzuru Ninoyu Eric Du Clara Draf Yun Zhang Uri Manor Richard H. Scheuermann Richard H. Scheuermann Rick Friedman |
| author_facet | Ely Cheikh Boussaty Neil Tedeschi Mark Novotny Yuzuru Ninoyu Eric Du Clara Draf Yun Zhang Uri Manor Richard H. Scheuermann Richard H. Scheuermann Rick Friedman |
| author_sort | Ely Cheikh Boussaty |
| collection | DOAJ |
| description | 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,1 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. |
| first_indexed | 2024-03-09T14:15:19Z |
| format | Article |
| id | doaj.art-fe06f769e4d24d9f9b0b1d86f5294812 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-03-09T14:15:19Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-fe06f769e4d24d9f9b0b1d86f52948122023-11-29T04:41:30ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022023-11-011710.3389/fncel.2023.12566191256619Cochlear transcriptome analysis of an outbred mouse population (CFW)Ely Cheikh Boussaty0Neil Tedeschi1Mark Novotny2Yuzuru Ninoyu3Eric Du4Clara Draf5Yun Zhang6Uri Manor7Richard H. Scheuermann8Richard H. Scheuermann9Rick Friedman10Department of Otolaryngology, University of California, San Diego, La Jolla, CA, United StatesJ. Craig Venter Institute, La Jolla, CA, United StatesJ. Craig Venter Institute, La Jolla, CA, United StatesDepartment of Otolaryngology, University of California, San Diego, La Jolla, CA, United StatesDepartment of Otolaryngology, University of California, San Diego, La Jolla, CA, United StatesDepartment of Otolaryngology, University of California, San Diego, La Jolla, CA, United StatesJ. Craig Venter Institute, La Jolla, CA, United StatesDepartment of Cell and Developmental Biology, University of California San Diego, Salk Institute for Biological Studies, Waitt Advanced Biophotonics Center, La Jolla, CA, United StatesJ. Craig Venter Institute, La Jolla, CA, United StatesDepartment of Pathology, University of California, San Diego, La Jolla, CA, United StatesDepartment of Otolaryngology, University of California, San Diego, La Jolla, CA, United StatesAge-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,1 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.https://www.frontiersin.org/articles/10.3389/fncel.2023.1256619/fullsingle nucleus RNA sequencingcell ontologymarker genesage-related hearing lossgenetic determinants of hearing loss |
| spellingShingle | Ely Cheikh Boussaty Neil Tedeschi Mark Novotny Yuzuru Ninoyu Eric Du Clara Draf Yun Zhang Uri Manor Richard H. Scheuermann Richard H. Scheuermann Rick Friedman Cochlear transcriptome analysis of an outbred mouse population (CFW) Frontiers in Cellular Neuroscience single nucleus RNA sequencing cell ontology marker genes age-related hearing loss genetic determinants of hearing loss |
| title | Cochlear transcriptome analysis of an outbred mouse population (CFW) |
| title_full | Cochlear transcriptome analysis of an outbred mouse population (CFW) |
| title_fullStr | Cochlear transcriptome analysis of an outbred mouse population (CFW) |
| title_full_unstemmed | Cochlear transcriptome analysis of an outbred mouse population (CFW) |
| title_short | Cochlear transcriptome analysis of an outbred mouse population (CFW) |
| title_sort | cochlear transcriptome analysis of an outbred mouse population cfw |
| topic | single nucleus RNA sequencing cell ontology marker genes age-related hearing loss genetic determinants of hearing loss |
| url | https://www.frontiersin.org/articles/10.3389/fncel.2023.1256619/full |
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