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 dy...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 ceils 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 sVatrophyand hencedelay theprogressionofARHL.展开更多
基金supported by the National Key Research and Development Program of China(No.2020YFA0804000)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDA16000000)+12 种基金the National Natural Science Foundation of China(Nos.82192863,81921006,92149301,92168201,91949209,92049304,82125011,82122024,82071588,92049116,32121001,32000500,82030029,81970882,31900523,82271600,32200610,and 81861168034)the National Key Research and Development Program of China(Nos.2018YFC2000100,2021ZD0202400,2020YFA0112200,2018YFA0107203,2021YFF1201005,and2019YFA0110100)the Program of the Beijing Natural Science Foundation(No.Z190019)CAS Project for Young Scientists in Basic Research(No.YSBR-076 and YSBR-012)the Key Research Program of the Chinese Academy of Sciences(No.KFZD-SW-221)K.C.Wong Education Foundation(Nos.GJTD-2019-06 and GJTD-2019-08)Youth Innovation Promotion Association of CAS(Nos.2021078,2022083,and E1CAZW0401)Young Elite Scientists Sponsorship Program by CAST(Nos.YESS20200012 and YESS20210002)the State Key Laboratory of Stem Cell and Reproductive Biology,the State Key Laboratory of Membrane Biology,the Tencent Foundation(No.2021-1045)the Informatization Plan of Chinese Academy of Sciences(Nos.CAS-WX2021SF-0301 and CASWX2022SDC-XK14)the Pilot Project for Public Welfare Development and Reform of Beijing-affliated Medical Research Institutes(No.11000022T000000461062)Natural Science Foundation from Jiangsu Province(No.BE2019711),Shenzhen Fundamental Research Program(No.JCYJ20190814093401920)Open Research Fund of State Key Laboratory of Genetic Engineering,Fudan University(No.SKLGE-2109).
文摘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 ceils 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 sVatrophyand hencedelay theprogressionofARHL.
