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CHIT1-positive microglia drive motor neuron aging in the primate spinal cord

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收录情况： ◇ SCIE ◇ 自然指数

作者：
Shuhui Sun[1,2,3,4] * ; Jiaming Li[5,6] * ; Si Wang[7,8,9,10] * ; Jingyi Li[1,3,4,6,9] * ; Jie Ren[3,5,6,9,11] * ; Zhaoshi Bao[12,13] * ; Le Sun[14] * ; Xibo Ma[15,16,17] * ; Fangshuo Zheng[10] ; Shuai Ma[1,3,4,6,9] ; Liang Sun[9,18] ; Min Wang[2,19] ; Yan Yu[1,6] ; Miyang Ma[1,6] ; Qiaoran Wang[5,6] ; Zhiyuan Chen[15,16] ; He Ma[15,17] ; Xuebao Wang[2,6] ; Zeming Wu[1,3,4] ; Hui Zhang[1,6] ; Kaowen Yan[1,3,4] ; Yuanhan Yang[1,6] ; Yixin Zhang[2,6] ; Sheng Zhang[1,6] ; Jinghui Lei[7,8] ; Zhao-Qian Teng[2,3,4,6] ; Chang-Mei Liu[2,3,4,6] ; Ge Bai[20] ; Yan-Jiang Wang[9,21,22] ; Jian Li[9,18] ; Xiaoqun Wang[14,23] ; Guoguang Zhao[24,25,26] ; Tao Jiang[12,13,27] ; Juan Carlos Izpisua Belmonte[28] ; Jing Qu[2,3,4,6,9] ; Weiqi Zhang[3,5,6,9] ; Guang-Hui Liu[1,3,4,6,7,8,9] ;
机构： [1]State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy ofSciences, Beijing, China [2]State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology, Chinese Academy of Sciences, Beijing, China [3]Institute for Stem Celland Regeneration, Chinese Academy of Sciences, Beijing, China [4]Beijing Institute for StemCell and Regenerative Medicine, Beijing, China [5]CAS Key Laboratory of Genomic andPrecision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and ChinaNational Center for Bioinformation, Beijing, China [6]University of Chinese Academy ofSciences, Beijing, China [7]Advanced Innovation Center for Human Brain Protection, andNational Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital MedicalUniversity, Beijing, China [8]Aging Translational Medicine Center, International Center forAging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital,Capital Medical University, Beijing, China [9]Aging Biomarker Consortium, Beijing, China [10]The Fifth People’s Hospital of Chongqing, Chongqing, China [11]Key Laboratory of RNAScience and Engineering, Beijing Institute of Genomics, Chinese Academy of Sciences andChina National Center for Bioinformation, Beijing, China [12]Department of Neurosurgery,Beijing Tiantan Hospital, Capital Medical University, Beijing, China [13]The Chinese GliomaGenome Atlas, Beijing, China [14]Beijing Institute of Brain Disorders, Capital Medical University,Beijing, China [15]MAIS, State Key Laboratory of Multimodal Artificial Intelligence Systems,Institute of Automation, Chinese Academy of Sciences, Beijing, China [16]School of ArtificialIntelligence, University of Chinese Academy of Sciences, Beijing, China [17]College ofMedicine and Biomedical Information Engineering, Northeastern University, Shenyang, China [18]The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology,Beijing, China [19]University of Science and Technology of China, Hefei, China [20]The MOEFrontier Research Center of Brain & Brain-Machine Integration, Zhejiang University School ofBrain Science and Brain Medicine, Hangzhou, China [21]Department of Neurology, DapingHospital, Third Military Medical University, Chongqing, China [22]State Key Laboratory ofTrauma and Chemical Poisoning, Daping Hospital, Third Military Medical University,Chongqing, China [23]State Key Laboratory of Cognitive Neuroscience and Learning, IDG/McGovern Institute for Brain Research, New Cornerstone Science Laboratory, Beijing NormalUniversity, Beijing, China [24]Department of Neurosurgery, Xuanwu Hospital Capital MedicalUniversity, Beijing, China [25]Clinical Research Center for Epilepsy Capital Medical University,Beijing, China [26]Beijing Municipal Geriatric Medical Research Center, Beijing, China [27]BeijingNeurosurgical Institute, Beijing, China [28]Altos Labs, San Diego, CA, USA
出处：
DOI： 10.1038/s41586-023-06783-1
ISSN：

摘要：
Aging is a critical factor in spinal cord-associated disorders1, yet aging-specific mechanisms underlying this relationship remain poorly understood. To address this knowledge gap, we combined single-nucleus RNA sequencing with behavioral and neurophysiological analysis in non-human primates (NHPs). We identified motor neuron senescence and neuroinflammation with microglial hyperactivation as intertwined hallmarks of spinal cord aging. As an underlying mechanism, we identified a previously unreported neurotoxic microglial state demarcated by elevated expression of CHIT1 (a secreted mammalian chitinase) specific to the aged spinal cords in NHP and human biopsies. In the aged spinal cord, CHIT1-positive microglia preferentially localize around motor neurons (MNs), and they are capable of triggering senescence, partly by activating SMAD signaling. We further validated the driving role of secreted CHIT1 on MN senescence by multi-modal experiments both in vivo, utilizing the NHP spinal cord as a model and in vitro, employing a sophisticated human MN-and-microenvironment interplay modeling system. Moreover, we demonstrated that ascorbic acid, a geroprotective compound, counteracted the pro-senescent effect of CHIT1 and mitigated motor neuron senescence in aged monkeys. Our findings provide the first single-cell resolution cellular and molecular landscape of the aged primate spinal cord and identify a new biomarker and intervention target for spinal cord degeneration.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.

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外文
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中科院(CAS)分区：
出版当年[2022]版：
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
最新[2023]版：
大类 | 1 区 综合性期刊
小类 | 1 区 综合性期刊
JCR分区：
出版当年[2021]版：
Q1 MULTIDISCIPLINARY SCIENCES
最新[2023]版：
Q1 MULTIDISCIPLINARY SCIENCES

影响因子： 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者机构： [1]State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy ofSciences, Beijing, China [2]State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology, Chinese Academy of Sciences, Beijing, China [3]Institute for Stem Celland Regeneration, Chinese Academy of Sciences, Beijing, China [4]Beijing Institute for StemCell and Regenerative Medicine, Beijing, China
共同第一作者：
通讯作者：
通讯机构： [1]State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy ofSciences, Beijing, China [2]State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology, Chinese Academy of Sciences, Beijing, China [3]Institute for Stem Celland Regeneration, Chinese Academy of Sciences, Beijing, China [4]Beijing Institute for StemCell and Regenerative Medicine, Beijing, China [5]CAS Key Laboratory of Genomic andPrecision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences and ChinaNational Center for Bioinformation, Beijing, China [6]University of Chinese Academy ofSciences, Beijing, China [7]Advanced Innovation Center for Human Brain Protection, andNational Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital MedicalUniversity, Beijing, China [8]Aging Translational Medicine Center, International Center forAging and Cancer, Beijing Municipal Geriatric Medical Research Center, Xuanwu Hospital,Capital Medical University, Beijing, China [9]Aging Biomarker Consortium, Beijing, China
推荐引用方式(GB/T 7714)：
Shuhui Sun,Jiaming Li,Si Wang,et al.CHIT1-positive microglia drive motor neuron aging in the primate spinal cord[J].NATURE.2023,624(7992):611-+.doi:10.1038/s41586-023-06783-1.
APA：
Shuhui Sun,Jiaming Li,Si Wang,Jingyi Li,Jie Ren...&Guang-Hui Liu.(2023).CHIT1-positive microglia drive motor neuron aging in the primate spinal cord.NATURE,624,(7992)
MLA：
Shuhui Sun,et al."CHIT1-positive microglia drive motor neuron aging in the primate spinal cord".NATURE 624..7992(2023):611-+

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