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Single-cell transcriptome analysis of aging mouse liver

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单位: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Expt Med Ctr, Wuhan, Peoples R China [2]Huazhong Univ Sci & Technol, Tongji Hosp, Key Lab Vasc Aging, Minist Educ,Tongji Med Coll, Wuhan, Peoples R China [3]Wuhan Fourth Hosp, Wuhan, Peoples R China [4]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Geriatr, Wuhan, Peoples R China [5]Sun Yat sen Univ, Sun Yat sen Mem Hosp, Dept Biliopancreat Surg, Guangzhou, Peoples R China [6]Sun Yat sen Univ, Sun Yat sen Mem Hosp, Guangdong Prov Key Lab Malignant Tumor Epigenet &, Guangzhou, Peoples R China [7]Anhui Med Univ, Dept Pathophysiol, Hefei, Peoples R China [8]Anhui Med Univ, Dept Pathophysiol, Hefei 230032, Anhui, Peoples R China [9]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Expt Med Ctr, 1095 Jiefang Ave, Wuhan 430030, Hubei, Peoples R China
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关键词: aging inflammation liver single-cell RNA sequencing

摘要:
Aging has a great impact on the liver, which causes a loss of physiological integrity and an increase in susceptibility to injury, but many of the underlying molecular and cellular processes remain unclear. Here, we performed a comprehensive single-cell transcriptional profiling of the liver during aging. Our data showed that aging affected the cellular composition of the liver. The increase in inflammatory cells including neutrophils and monocyte-derived macrophages, as well as in inflammatory cytokines, could indicate an inflammatory tissue microenvironment in aged livers. Moreover, aging drove a distinct transcriptional course in each cell type. The commonly significant up-regulated genes were S100a8, S100a9, and RNA-binding motif protein 3 across all cell types. Aging-related pathways such as biosynthesis, metabolism, and oxidative stress were up-regulated in aged livers. Additionally, key ligand-receptor pairs for intercellular communication, primarily linked to macrophage migration inhibitory factor, transforming growth factor-beta, and complement signaling, were also elevated. Furthermore, hepatic stellate cells (HSCs) serve as the prominent hub for intrahepatic signaling. HSCs acquired an "activated" phenotype, which may be involved in the increased intrahepatic vascular tone and fibrosis with aging. Liver sinusoidal endothelial cells derived from aged livers were pseudocapillarized and procontractile, and exhibited down-regulation of genes involved in vascular development and homeostasis. Moreover, the aging-related changes in cellular composition and gene expression were reversed by caloric restriction. Collectively, the present study suggests liver aging is linked to a significant liver sinusoidal deregulation and a moderate pro-inflammatory state, providing a potential concept for understanding the mechanism of liver aging. Extensive single-cell sequencing is performed to chart the landscape of mouse liver aging. The study paints a detailed picture of the changes in cellular compositions, gene expressions, cellular pathways, and intercellular communications across different cell types with age. (Graphical abstract was drawn by Figdraw 2.0.)image

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出版当年[2023]版:
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学 2 区 生物学 3 区 细胞生物学
最新[2025]版:
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学 2 区 生物学 3 区 细胞生物学
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出版当年[2022]版:
Q1 BIOLOGY Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Q2 CELL BIOLOGY
最新[2023]版:
Q1 BIOLOGY Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Q2 CELL BIOLOGY

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

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第一作者单位: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Expt Med Ctr, Wuhan, Peoples R China [2]Huazhong Univ Sci & Technol, Tongji Hosp, Key Lab Vasc Aging, Minist Educ,Tongji Med Coll, Wuhan, Peoples R China
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通讯机构: [1]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Expt Med Ctr, Wuhan, Peoples R China [2]Huazhong Univ Sci & Technol, Tongji Hosp, Key Lab Vasc Aging, Minist Educ,Tongji Med Coll, Wuhan, Peoples R China [7]Anhui Med Univ, Dept Pathophysiol, Hefei, Peoples R China [8]Anhui Med Univ, Dept Pathophysiol, Hefei 230032, Anhui, Peoples R China [9]Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Expt Med Ctr, 1095 Jiefang Ave, Wuhan 430030, Hubei, Peoples R China
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