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Protein Cell    2021, Vol. 12 Issue (9) : 695-716    https://doi.org/10.1007/s13238-021-00852-9
RESEARCH ARTICLE
Single-nucleus transcriptomic landscape of primate hippocampal aging
Hui Zhang1,6, Jiaming Li4,6,7,10,11, Jie Ren4,5,6,7,10, Shuhui Sun1,5,13, Shuai Ma1,5,13, Weiqi Zhang4,5,6,7,10, Yang Yu12,14, Yusheng Cai1,5,13, Kaowen Yan1,5,13, Wei Li2,5,6,13, Baoyang Hu2,5,6,13, Piu Chan3, Guo-Guang Zhao3,9, Juan Carlos Izpisua Belmonte15, Qi Zhou2,5,6,13, Jing Qu2,5,6,13(), Si Wang3,8(), Guang-Hui Liu1,3,5,6,13()
1. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
2. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
3. Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing 100053, China
4. CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China
5. Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China
6. University of Chinese Academy of Sciences, Beijing 100049, China
7. China National Center for Bioinformation, Beijing 100101, China
8. Aging Translational Medicine Center, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
9. Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
10. Sino-Danish College, University of Chinese Academy of Sciences, Beijing 101408, China
11. Sino-Danish Center for Education and Research, Beijing 101408, China
12. Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing 100191, China
13. Beijing Institute for Stem Cell and Regenerative Medicine, Beijing 100101, China
14. Stem Cell Research Center, Peking University Third Hospital, Beijing 100191, China
15. Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA
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Abstract

The hippocampus plays a crucial role in learning and memory, and its progressive deteriorationwith age is functionally linked to a variety ofhuman 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 unction along the neurogenesis trajectory; additionally elevated pro-inflammatory responses in the agedmicroglia 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.
Keywords aging      hippocampus      primate      single-cell RNA sequencing     
Corresponding Author(s): Jing Qu,Si Wang,Guang-Hui Liu   
Online First Date: 30 July 2021    Issue Date: 14 October 2021
 Cite this article:   
Hui Zhang,Jiaming Li,Jie Ren, et al. Single-nucleus transcriptomic landscape of primate hippocampal aging[J]. Protein Cell, 2021, 12(9): 695-716.
 URL:  
https://academic.hep.com.cn/pac/EN/10.1007/s13238-021-00852-9
https://academic.hep.com.cn/pac/EN/Y2021/V12/I9/695
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