A single-nucleus transcriptomic atlas of primate liver aging uncovers the pro-senescence role of SREBP2 in hepatocytes

查看全文 作　　者：Shanshan [1,3,6]Yang;Chengyu [4,7]Liu;Mengmeng [2,8,9]Jiang;Xiaoqian [4,8,9]Liu;Lingling [1,3]Geng;Yiyuan [2,9]Zhang;Shuhui [2,8,9]Sun;Kang [2,7]Wang;jian [2,7]Yin;Shuai [2,8]Ma;Si [1,3]Wang;Juan Carlos Izpisua [11]Belmonte;Weiqi [5,7,8,10]Zhang;Jing [4,7,8,9,10]Qu;Guang-Hui [1,2,3,6,7,8,9,10]Liu

机构地区：[1]Advanced Innovation Center for Human Brain Protection and National Clinical Research Center for Geriatric Disorders,Xuanwu Hospital Capital Medical University,Beijing 100053,China;[2]State Key Laboratory of Membrane Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China;[3]Aging Translational Medicine Center,International Center for Aging and Cancer,Beijing Municipal Geriatric Medical Research Center,Xuanwu Hospital,Capital Medical University,Beijing 100053,China;[4]State Key Laboratory of Stem Cell and Reproductive Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China;[5]CAS Key Laboratory of Genomic and Precision Medicine,Beijing Institute of Genomics,Chinese Academy of Sciences and China National Center for Bioinformation,Beijing 100101,China;[6]Xuanwu Hospital Capital Medical University,Beijing 100053,China;[7]University of Chinese Academy of Sciences,Beijing 100049,China;[8]Institute for Stem Cell and Regeneration,Chinese Academy of Sciences,Beijing 100101,China;[9]Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China;[10]Aging Biomarker Consortium,Beijing 100101,China;[11]Altos Labs,Inc.,San Diego,CA 94022,USA+These authors contributed equally

出　　处：《Protein & Cell》索引2024年第15卷第2期,共23页

基　　金：supported by the National Key Research and Development Program of China (Grant Nos.2022YFA1103700,2020YFA0804000,2020YFA0112200,2021YFF1201000,2022YFA1103800,2021YFA1101401,the STI2030-Major Projects-2021ZD0202400);the National Natural Science Foundation of China (Grant Nos.92049116,81921006,82125011,92149301,92168201,91949209,92049304,32121001,82192863,82122024,82071588,32000500,82271600);the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16000000);CAS Project for Young Scientists in Basic Research (YSBR-076,YSBR-012);the Program of the Beijing Natural Science Foundation (Z190019);the Pilot Project for Public Welfare Development and Reform of Beijing-affiliated Medical Research Institutes (No.11000022T000000461062);Youth Innovation Promotion Association of CAS (E1CAZW0401,2023092,2022083);Young Elite Scientists Sponsorship Program by CAST (YESS20200012,YESS20210002);the Informatization Plan of Chinese Academy of Sciences (CAS-WX2021SF-0301,CAS-WX2022SDC-XK14,CAS-WX2021SF-0101);New Cormerstone Science Foundation through the XPLORER PRIZE (2021-1045);Excellent Young Talents Program of Capital Medical University (No.12300927);Excellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team (BPHR202203105). 摘　　要：Aging increases the risk ofliver diseases and systemic susceptibility to aging-related diseases.However,cell type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely characterized.Here,we constructed the first single-nucleus transcriptomic landscape of primate liver aging,in which we resolved cell type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell-cell interactions between hepatocytes and niche cells.Upon in-depth dissection of this rich dataset,we identifed impaired lipid metabolism and upregulation of chronic inflammation-related genes prominently associated with declined liver functions during aging.In particular,hyperactivated sterol regulatory element-binding protein(SREBP)signaling was a hallmark of the aged liver,and consequently,forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes,manifesting as impaired detoxification and accelerated cellular senescence.This study expands our knowledge of primate liver aging and informs the development of diagnostics and therapeutic interventions for liver aging and associated diseases. 关键词：single-nucleus RNA sequencing LIVER HEPATOCYTES AGING SENESCENCE SREBP2

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A single-nucleus transcriptomic atlas of primate liver aging uncovers the pro-senescence role of SREBP2 in hepatocytes

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