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In silico Single-Cell Analysis of Steroid-Responsive Gene Targets in the Mammalian Cochlea
BACKGROUND: Treatment of many types of hearing instability in humans, including sudden sensorineural hearing loss, Meniere's disease, and autoimmune inner ear disease, rely heavily on the utilization of corticosteroids delivered both by oral and transtympanic routes. Despite this use, there is...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8821961/ https://www.ncbi.nlm.nih.gov/pubmed/35145472 http://dx.doi.org/10.3389/fneur.2021.818157 |
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author | Nelson, Lacey Lovett, Braeden Johns, J. Dixon Gu, Shoujun Choi, Dongseok Trune, Dennis Hoa, Michael |
author_facet | Nelson, Lacey Lovett, Braeden Johns, J. Dixon Gu, Shoujun Choi, Dongseok Trune, Dennis Hoa, Michael |
author_sort | Nelson, Lacey |
collection | PubMed |
description | BACKGROUND: Treatment of many types of hearing instability in humans, including sudden sensorineural hearing loss, Meniere's disease, and autoimmune inner ear disease, rely heavily on the utilization of corticosteroids delivered both by oral and transtympanic routes. Despite this use, there is heterogeneity in the response to treatment with corticosteroids in humans with these diseases. The mechanisms by which corticosteroids exert their effect and the cell types in which they exert their effects in the inner ear remain poorly characterized. In this study, we localize steroid-responsive genes to cochlear cell types using previously published transcriptome datasets from the mammalian cochlea. METHODS: Steroid-responsive genes were localized to specific cochlear cell types using existing transcriptome datasets from wild-type mammalian cochlea exposed to systemic and transtympanic steroids, as well as previously published single-cell and single-nucleus RNA-sequencing datasets from the mammalian cochlea. Gene ontology (GO) analysis of differentially expressed genes (DEGs) was performed using PANTHER to investigate cellular processes implicated in transtympanic vs. systemic steroid action in the cochlea. RESULTS: Steroid-responsive genes were localized to specific cell types and regions in the cochlea including the stria vascularis, organ of Corti, and spiral ganglion neurons (SGN). Analyses demonstrate differential prevalence of steroid-responsive genes. GO analysis demonstrated steroid-responsive DEGs in the SGN to be associated with angiogenesis, apoptosis, and cytokine-mediated anti-inflammatory pathways. CONCLUSIONS: Single-cell and single-nucleus transcriptome datasets localize steroid-responsive genes to specific regions in the cochlea. Further study of these regionally-specific steroid-responsive genes may provide insight into the mechanisms of and clinical response to corticosteroids in diseases of hearing instability. |
format | Online Article Text |
id | pubmed-8821961 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-88219612022-02-09 In silico Single-Cell Analysis of Steroid-Responsive Gene Targets in the Mammalian Cochlea Nelson, Lacey Lovett, Braeden Johns, J. Dixon Gu, Shoujun Choi, Dongseok Trune, Dennis Hoa, Michael Front Neurol Neurology BACKGROUND: Treatment of many types of hearing instability in humans, including sudden sensorineural hearing loss, Meniere's disease, and autoimmune inner ear disease, rely heavily on the utilization of corticosteroids delivered both by oral and transtympanic routes. Despite this use, there is heterogeneity in the response to treatment with corticosteroids in humans with these diseases. The mechanisms by which corticosteroids exert their effect and the cell types in which they exert their effects in the inner ear remain poorly characterized. In this study, we localize steroid-responsive genes to cochlear cell types using previously published transcriptome datasets from the mammalian cochlea. METHODS: Steroid-responsive genes were localized to specific cochlear cell types using existing transcriptome datasets from wild-type mammalian cochlea exposed to systemic and transtympanic steroids, as well as previously published single-cell and single-nucleus RNA-sequencing datasets from the mammalian cochlea. Gene ontology (GO) analysis of differentially expressed genes (DEGs) was performed using PANTHER to investigate cellular processes implicated in transtympanic vs. systemic steroid action in the cochlea. RESULTS: Steroid-responsive genes were localized to specific cell types and regions in the cochlea including the stria vascularis, organ of Corti, and spiral ganglion neurons (SGN). Analyses demonstrate differential prevalence of steroid-responsive genes. GO analysis demonstrated steroid-responsive DEGs in the SGN to be associated with angiogenesis, apoptosis, and cytokine-mediated anti-inflammatory pathways. CONCLUSIONS: Single-cell and single-nucleus transcriptome datasets localize steroid-responsive genes to specific regions in the cochlea. Further study of these regionally-specific steroid-responsive genes may provide insight into the mechanisms of and clinical response to corticosteroids in diseases of hearing instability. Frontiers Media S.A. 2022-01-25 /pmc/articles/PMC8821961/ /pubmed/35145472 http://dx.doi.org/10.3389/fneur.2021.818157 Text en Copyright © 2022 Nelson, Lovett, Johns, Gu, Choi, Trune and Hoa. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neurology Nelson, Lacey Lovett, Braeden Johns, J. Dixon Gu, Shoujun Choi, Dongseok Trune, Dennis Hoa, Michael In silico Single-Cell Analysis of Steroid-Responsive Gene Targets in the Mammalian Cochlea |
title | In silico Single-Cell Analysis of Steroid-Responsive Gene Targets in the Mammalian Cochlea |
title_full | In silico Single-Cell Analysis of Steroid-Responsive Gene Targets in the Mammalian Cochlea |
title_fullStr | In silico Single-Cell Analysis of Steroid-Responsive Gene Targets in the Mammalian Cochlea |
title_full_unstemmed | In silico Single-Cell Analysis of Steroid-Responsive Gene Targets in the Mammalian Cochlea |
title_short | In silico Single-Cell Analysis of Steroid-Responsive Gene Targets in the Mammalian Cochlea |
title_sort | in silico single-cell analysis of steroid-responsive gene targets in the mammalian cochlea |
topic | Neurology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8821961/ https://www.ncbi.nlm.nih.gov/pubmed/35145472 http://dx.doi.org/10.3389/fneur.2021.818157 |
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