生物
神经科学
神经发生
小胶质细胞
海马结构
神经干细胞
转录组
干细胞
细胞生物学
炎症
免疫学
基因表达
遗传学
基因
作者
Hui Zhang,Jiaming Li,Jie Ren,Shuhui Sun,Shuai Ma,Weiqi Zhang,Yang Yu,Yusheng Cai,Yan Ke,Wei Li,Baoyang Hu,Piu Chan,Guoguang Zhao,Juan Carlos Izpisúa Belmonte,Qi Zhou,Jing Qu,Si Wang,Guanghui Liu
出处
期刊:Protein & Cell
[Springer Nature]
日期:2021-05-30
卷期号:12 (9): 695-716
被引量:52
标识
DOI:10.1007/s13238-021-00852-9
摘要
The hippocampus plays a crucial role in learning and memory, and its progressive deterioration with age is functionally linked to a variety of human neurodegenerative diseases. Yet a systematic profiling of the aging effects on various hippocampal cell types in primates is still missing. Here, we reported a variety of new aging-associated phenotypic changes of the primate hippocampus. These include, in particular, increased DNA damage and heterochromatin erosion with time, alongside loss of proteostasis and elevated inflammation. To understand their cellular and molecular causes, we established the first single-nucleus transcriptomic atlas of primate hippocampal aging. Among the 12 identified cell types, neural transiently amplifying progenitor cell (TAPC) and microglia were most affected by aging. In-depth dissection of gene-expression dynamics revealed impaired TAPC division and compromised neuronal function along the neurogenesis trajectory; additionally elevated pro-inflammatory responses in the aged microglia and oligodendrocyte, as well as dysregulated coagulation pathways in the aged endothelial cells may contribute to a hostile microenvironment for neurogenesis. This rich resource for understanding primate hippocampal aging may provide potential diagnostic biomarkers and therapeutic interventions against age-related neurodegenerative diseases.
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