Single-cell transcriptomic atlas of mouse cochlear aging

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摘要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 land-scape 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-re-lated SV atrophy and hence delay the progression of ARHL.

作者 Guoqiang Sun ^[1] Yandong Zheng ^[1] Xiaolong Fu ^[2] Weiqi Zhang ^[3] Jie Ren ^[4] Shuai Ma ^[5] Shuhui Sun ^[6] Xiaojuan He ^[7] Qiaoran Wang ^[8] Zhejun Ji ^[9] Fang Cheng ^[10] Kaowen Yan ^[6] Ziyi Liu ^[11] Juan Carlos Izpisua Belmonte ^[12] Jing Qu ^[13] Si Wang ^[14] Renjie Chai ^[15] Guang-Hui Liu ^[16] 学术成果认领

作者单位 State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China;University of Chinese Academy of Sciences,Beijing 100049,China ^[1] State Key Laboratory of Bioelectronics,Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research,School of Life Sciences and Technology,Southeast University,Nanjing 211189,China ^[2] CAS Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,Chinese Academy of Sciences,Beijing 100101,China;Aging Translational Medicine Center,International Center for Aging and Cancer,Beijing Municipal Geriatric Medical Research Center,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;University of Chinese Academy of Sciences,Beijing 100049,China;Institute for Stem Cell and Regeneration,CAS,Beijing 100101,China;China National Center for Bioinformation,Beijing 100101,China ^[3] CAS Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,Chinese Academy of Sciences,Beijing 100101,China;University of Chinese Academy of Sciences,Beijing 100049,China;Institute for Stem Cell and Regeneration,CAS,Beijing 100101,China;China National Center for Bioinformation,Beijing 100101,China ^[4] State Key Laboratory of Membrane Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China;Institute for Stem Cell and Regeneration,CAS,Beijing 100101,China;Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China;The Fifth People's Hospital of Chongqing,Chongqing 400062,China ^[5] State Key Laboratory of Membrane Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China;Institute for Stem Cell and Regeneration,CAS,Beijing 100101,China;Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China ^[6] Advanced Innovation Center for Human Brain Protection,National Clinical Research Center for Geriatric Disorders,Xuanwu Hospital Capital Medical University,Beijing 100053,China ^[7] CAS Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,Chinese Academy of Sciences,Beijing 100101,China;University of Chinese Academy of Sciences,Beijing 100049,China;China National Center for Bioinformation,Beijing 100101,China ^[8] State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China;Institute for Stem Cell and Regeneration,CAS,Beijing 100101,China;Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China ^[9] National Laboratory of Biomacromolecules,CAS Center for Excellence in Biomacromolecules,Institute of Biophysics,Chinese Academy of Sciences,Beijing 100101,China;University of Chinese Academy of Sciences,Beijing 100049,China ^[10] Shandong Provincial Hospital and School of Laboratory Animal Science,Shandong First Medical University,Jinan 250000,China ^[11] Gene Expression Laboratory,Salk Institute for Biological Studies,La Jolla,CA 92037,USA ^[12] State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China;University of Chinese Academy of Sciences,Beijing 100049,China;Institute for Stem Cell and Regeneration,CAS,Beijing 100101,China;Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China ^[13] Advanced Innovation Center for Human Brain Protection,National Clinical Research Center for Geriatric Disorders,Xuanwu Hospital Capital Medical University,Beijing 100053,China;Aging Translational Medicine Center,International Center for Aging and Cancer,Beijing Municipal Geriatric Medical Research Center,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;The Fifth People's Hospital of Chongqing,Chongqing 400062,China ^[14] State Key Laboratory of Bioelectronics,Jiangsu Province High-Tech Key Laboratory for Bio-Medical Research,School of Life Sciences and Technology,Southeast University,Nanjing 211189,China;Institute for Stem Cell and Regeneration,CAS,Beijing 100101,China;Co-Innovation Center of Neuroregeneration,Nantong University,Nantong 226001,China ^[15] State Key Laboratory of Membrane Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China;Advanced Innovation Center for Human Brain Protection,National Clinical Research Center for Geriatric Disorders,Xuanwu Hospital Capital Medical University,Beijing 100053,China;University of Chinese Academy of Sciences,Beijing 100049,China;Institute for Stem Cell and Regeneration,CAS,Beijing 100101,China;Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China ^[16]

关键词 single-cell transcriptomic atlas mouse cochlea aging

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RESEARCH ARTICLES

发布时间 2023-06-30

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