Single-cell transcriptomic atlas of mouse cochlear aging

Guoqiang Sun; Yandong Zheng; Xiaolong Fu; Weiqi Zhang; Jie Ren; Shuai Ma; Shuhui Sun; Xiaojuan He; Qiaoran Wang; Zhejun Ji; Fang Cheng; Kaowen Yan; Ziyi Liu; Juan Carlos Izpisua Belmonte; Jing Qu; Si Wang; Renjie Chai; Guang Hui Liu

doi:10.1093/procel/pwac058

Single-cell transcriptomic atlas of mouse cochlear aging

Guoqiang Sun, Yandong Zheng, Xiaolong Fu, Weiqi Zhang, Jie Ren, Shuai Ma, Shuhui Sun, Xiaojuan He, Qiaoran Wang, Zhejun Ji, Fang Cheng, Kaowen Yan, Ziyi Liu, Juan Carlos Izpisua Belmonte, Jing Qu^*, Si Wang^*, Renjie Chai^*, Guang Hui Liu^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

25 Citations (Scopus)

Abstract

Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.

Original language	English
Pages (from-to)	180-201
Number of pages	22
Journal	Protein and Cell
Volume	14
Issue number	3
DOIs	https://doi.org/10.1093/procel/pwac058
Publication status	Published - 1 Mar 2023
Externally published	Yes

Keywords

aging
cochlea
mouse
single-cell transcriptomic atlas

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10.1093/procel/pwac058

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title = "Single-cell transcriptomic atlas of mouse cochlear aging",

abstract = "Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.",

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author = "Guoqiang Sun and Yandong Zheng and Xiaolong Fu and Weiqi Zhang and Jie Ren and Shuai Ma and Shuhui Sun and Xiaojuan He and Qiaoran Wang and Zhejun Ji and Fang Cheng and Kaowen Yan and Ziyi Liu and Belmonte, {Juan Carlos Izpisua} and Jing Qu and Si Wang and Renjie Chai and Liu, {Guang Hui}",

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year = "2023",

month = mar,

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doi = "10.1093/procel/pwac058",

language = "English",

volume = "14",

pages = "180--201",

journal = "Protein and Cell",

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TY - JOUR

T1 - Single-cell transcriptomic atlas of mouse cochlear aging

AU - Sun, Guoqiang

AU - Zheng, Yandong

AU - Fu, Xiaolong

AU - Zhang, Weiqi

AU - Ren, Jie

AU - Ma, Shuai

AU - Sun, Shuhui

AU - He, Xiaojuan

AU - Wang, Qiaoran

AU - Ji, Zhejun

AU - Cheng, Fang

AU - Yan, Kaowen

AU - Liu, Ziyi

AU - Belmonte, Juan Carlos Izpisua

AU - Qu, Jing

AU - Wang, Si

AU - Chai, Renjie

AU - Liu, Guang Hui

PY - 2023/3/1

Y1 - 2023/3/1

N2 - Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.

AB - Progressive functional deterioration in the cochlea is associated with age-related hearing loss (ARHL). However, the cellular and molecular basis underlying cochlear aging remains largely unknown. Here, we established a dynamic single-cell transcriptomic landscape of mouse cochlear aging, in which we characterized aging-associated transcriptomic changes in 27 different cochlear cell types across five different time points. Overall, our analysis pinpoints loss of proteostasis and elevated apoptosis as the hallmark features of cochlear aging, highlights unexpected age-related transcriptional fluctuations in intermediate cells localized in the stria vascularis (SV) and demonstrates that upregulation of endoplasmic reticulum (ER) chaperon protein HSP90AA1 mitigates ER stress-induced damages associated with aging. Our work suggests that targeting unfolded protein response pathways may help alleviate aging-related SV atrophy and hence delay the progression of ARHL.

KW - aging

KW - cochlea

KW - mouse

KW - single-cell transcriptomic atlas

UR - http://www.scopus.com/inward/record.url?scp=85148367130&partnerID=8YFLogxK

U2 - 10.1093/procel/pwac058

DO - 10.1093/procel/pwac058

M3 - Article

C2 - 36933008

AN - SCOPUS:85148367130

SN - 1674-800X

VL - 14

SP - 180

EP - 201

JO - Protein and Cell

JF - Protein and Cell

IS - 3

ER -

Single-cell transcriptomic atlas of mouse cochlear aging

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