TY - JOUR
T1 - In silico Single-Cell Analysis of Steroid-Responsive Gene Targets in the Mammalian Cochlea
AU - Nelson, Lacey
AU - Lovett, Braeden
AU - Johns, J. Dixon
AU - Gu, Shoujun
AU - Choi, Dongseok
AU - Trune, Dennis
AU - Hoa, Michael
N1 - Publisher Copyright:
Copyright © 2022 Nelson, Lovett, Johns, Gu, Choi, Trune and Hoa.
PY - 2022/1/25
Y1 - 2022/1/25
N2 - 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.
AB - 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.
KW - RNA-Seq
KW - corticosteroids
KW - organ of Corti
KW - single cell RNA seq
KW - spiral ganglion neurons (SGN)
KW - stria vasularis
KW - sudden sensorineunal hearing loss
KW - transtympanic steroids
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U2 - 10.3389/fneur.2021.818157
DO - 10.3389/fneur.2021.818157
M3 - Article
AN - SCOPUS:85124342367
SN - 1664-2295
VL - 12
JO - Frontiers in Neurology
JF - Frontiers in Neurology
M1 - 818157
ER -