灵长类动物肝脏衰老的单核转录组图谱揭示了SREBP2在肝细胞中的促衰老作用

衰老会增加患肝脏疾病的风险和对衰老相关疾病的全身易感性。然而，高等脊椎动物的细胞类型特异性变化和肝脏衰老的潜在机制仍不完全表征。在这里，我们构建了灵长类动物肝脏衰老的第一个单核转录组景观，其中我们解决了三种肝细胞中细胞类型特异性基因表达的波动，并检测了肝细胞和生态位细胞之间的异常细胞间相互作用。在深入剖析这个丰富的数据集后，我们发现了脂质代谢受损和慢性炎症相关基因的上调，这些基因与衰老过程中肝功能下降密切相关。特别是，过度活化的甾醇调节元件结合蛋白（SREBP）信号传导是衰老肝脏的标志，因此，人原代肝细胞中SREBP2的强制激活在体内衰老表型中重现，表现为解毒受损和细胞衰老加速。这项研究扩展了我们对灵长类动物肝脏衰老的了解，并为肝脏衰老和相关疾病的诊断和治疗干预措施的发展提供了信息。

Aging increases the risk of liver diseases and systemic susceptibility to aging-related diseases. However, cell type-specific alterations and the underlying mechanisms 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 the cell type-specific fluctuations in gene expression among three types of hepatocytes and detected abnormal intercellular interactions between hepatocytes and niche cells. After in-depth analysis of this rich dataset, we identified impaired lipid metabolism and upregulation of genes associated with chronic inflammation, which are closely correlated with the decline of liver function during aging. Specifically, overactivated Sterol Regulatory Element-Binding Protein (SREBP) signaling is a hallmark of aging livers. Accordingly, forced activation of SREBP2 in human primary hepatocytes recapitulated in vivo aging phenotypes, characterized by impaired detoxification and accelerated cellular senescence. This study expands our understanding of primate liver aging and informs the development of diagnostic and therapeutic interventions for liver aging and related diseases.

搜集汇总

背景与挑战

背景概述

该数据集标题表明其聚焦于灵长类动物肝脏衰老的单核转录组研究，并探讨SREBP2在肝细胞中的促衰老作用，但详情页面中基本信息和数据表格均无实际内容，且存在系统错误提示，因此无法基于现有页面内容进行更具体的总结。