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

• DOI: 10.1093/procel/pwad039
• Publication Date: 2023-06-28T15:01:10Z
• Authors: Shanshan Yang; Chengyu Liu; Mengmeng Jiang; Xiaoqian Liu; Lingling Geng; Yiyuan Zhang; Shuhui Sun; Kang Wang; Jian Yin; Shuai Ma; Si Wang; Juan Carlos Izpis...; Weiqi Zhang; Jing Qu; Guang-Hui Liu
• Keywords: Senescence; Developmental Biology; Non human primate; Human genetics

Aging increases the risk of liver diseases and systemic susceptibility to aging-related diseases. However, cell type-specific changes underlying mechanism aging in higher vertebrates remain incompletely characterized. Here, we constructed first single-nucleus transcriptomic landscape primate aging, which resolved gene expression fluctuation hepatocytes across three zonations detected aberrant cell-cell interactions between niche cells. Upon in-depth dissection this rich dataset, identified impaired lipid metabolism upregulation chronic inflammation-related genes prominently associated with declined functions during aging. In particular, hyperactivated sterol regulatory element-binding protein (SREBP) signaling was a hallmark aged liver, consequently, forced activation SREBP2 human primary recapitulated vivo phenotypes, manifesting as detoxification accelerated cellular senescence. This study expands our knowledge informs development diagnostics therapeutic interventions for