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

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

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Agingincreases the risk of liver diseases and systemic susceptibility to aging-related diseases.However,cell type-spe-cific 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 iden-tified 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.

single-nucleus RNA sequencingliverhepatocytesagingsenescenceSREBP2

Shanshan Yang、Chengyu Liu、Mengmeng Jiang、Xiaoqian Liu、Lingling Geng、Yiyuan Zhang、Shuhui Sun、Kang Wang、Jian Yin、Shuai Ma、Si Wang、Juan Carlos Izpisua Belmonte、Weiqi Zhang、Jirig Qu、Guang-Hui Liu

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Advanced Innovation Center for Human Brain Protection and 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

Xuanwu Hospital Capital Medical University,Beijing 100053,China

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

State Key Laboratory of Membrane Biology,Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China

Institute for Stem Cell and Regeneration,Chinese Academy of Sciences,Beijing 100101,China

Beijing Institute for Stem Cell and Regenerative Medicine,Beijing 100101,China

Altos Labs,Inc.,San Diego,CA 94022,USA

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

Aging Biomarker Consortium,Beijing 100101,China

Xuanwu Hospital Capital Med

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National Key Re search and Development Program of ChinaNational Key Re search and Development Program of ChinaNational Key Re search and Development Program of ChinaNational Key Re search and Development Program of ChinaNational Key Re search and Development Program of ChinaNational Key Re search and Development Program of ChinaNational Key Re search and Development Program of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaStrategic Priority Research Program of the Chinese Academy of SciencesCAS Project for Young Scientists in Basic ResearchCAS Project for Young Scientists in Basic ResearchProgram of the Beijing Natural Science FoundationPilot Project for Public Welfare Development and Reform of Beijingaffiliated Medical Research InstitutesYouth Innovation Promotion Association of CASYouth Innovation Promotion Association of CASYouth Innovation Promotion Association of CASYoung Elite Scientists Sponsorship Program by CASTYoung Elite Scientists Sponsorship Program by CASTInformatization Plan of Chinese Academy of SciencesInformatization Plan of Chinese Academy of SciencesInformatization Plan of Chinese Academy of SciencesNew Cornerstone Science Foundation through the XPLORER PRIZE(2021-1045)Excellent Young Talents Program of Capital Medical UniversityExcellent Young Talents Training Program for the Construction of Beijing Municipal University Teacher Team

2022YFA11037002020YFA08040002020YFA01122002021YFF12010002022YFA11038002021YFA1101401the STI20392049116819210068212501192149301921682019194920992049304321210018219286382122024820715883XDA16000000YSBR-076YSBR-012Z19001911000022T000000461062E1CAZW040120230922022083YESS20200012YESS20210002CAS-WX2021SF-0301CAS-WX2022SDC-XK14CAS-WX2021SF-010112300927BPHR202203105

2024

10.1093/procel/pwad039

蛋白质与细胞

蛋白质与细胞

CSTPCD
影响因子：0.645
ISSN：
年,卷(期)：2024.15(2)
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