Single-nucleus transcriptomic landscape of primate hippocampal aging
Hui Zhang1,2, Jiaming Li3,2,4,5,6, Jie Ren3,7,2,4,5
1State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
Protein & Cell
|May 30, 2021
Summary
Aging primate hippocampi show increased DNA damage and inflammation. Neural progenitor cells and microglia are most affected, impacting learning and memory and offering targets for neurodegenerative disease therapies.
Area of Science:
- Neuroscience
- Cell Biology
- Genomics
Background:
- The hippocampus is vital for learning and memory.
- Aging impairs hippocampal function, linked to neurodegenerative diseases.
- Primate-specific aging profiles of hippocampal cells are lacking.
Purpose of the Study:
- To systematically profile aging effects on primate hippocampal cell types.
- To identify cellular and molecular mechanisms of hippocampal aging.
- To establish a single-nucleus transcriptomic atlas of primate hippocampal aging.
Main Methods:
- Single-nucleus RNA sequencing (snRNA-seq) on primate hippocampi.
- Analysis of 12 distinct hippocampal cell types.
- Gene expression dynamics and pathway analysis.
Main Results:
- Identified aging-associated DNA damage, heterochromatin erosion, proteostasis loss, and inflammation.
- Neural transiently amplifying progenitor cells (TAPC) and microglia showed significant aging effects.
- Impaired TAPC division, compromised neurogenesis, and heightened inflammation in aged cells were observed.
Conclusions:
- Primate hippocampal aging involves cellular damage and inflammatory responses.
- Aged microglia, oligodendrocytes, and endothelial cells create a detrimental microenvironment for neurogenesis.
- This atlas provides insights into biomarkers and therapies for age-related neurodegenerative diseases.
