Single-nucleus transcriptomic landscape of primate hippocampal aging.
10.1007/s13238-021-00852-9
- Author:
Hui ZHANG
1
;
Jiaming LI
2
;
Jie REN
2
;
Shuhui SUN
1
;
Shuai MA
1
;
Weiqi ZHANG
2
;
Yang YU
3
;
Yusheng CAI
1
;
Kaowen YAN
1
;
Wei LI
4
;
Baoyang HU
4
;
Piu CHAN
5
;
Guo-Guang ZHAO
5
;
Juan Carlos Izpisua BELMONTE
6
;
Qi ZHOU
4
;
Jing QU
7
;
Si WANG
8
;
Guang-Hui LIU
9
Author Information
1. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
2. CAS Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
3. Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Peking University Third Hospital, Beijing, 100191, China.
4. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
5. Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, 100053, China.
6. Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, CA, USA.
7. State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. qujing@ioz.ac.cn.
8. Advanced Innovation Center for Human Brain Protection, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital Capital Medical University, Beijing, 100053, China. wangsi@xwh.ccmu.edu.cn.
9. State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China. ghliu@ioz.ac.cn.
- Publication Type:Journal Article
- Keywords:
aging;
hippocampus;
primate;
single-cell RNA sequencing
- From:
Protein & Cell
2021;12(9):695-716
- CountryChina
- Language:English
-
Abstract:
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.
