Single-nucleus transcriptomic landscape of primate hippocampal aging.
|
IF: 15.328
|
Cited by: 32
|

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.

Keywords

Seurat
SHIELD
Spatial Transcriptomics
aging
hippocampus
primate
single-cell RNA sequencing

MeSH terms

Aging
Amyloid beta-Peptides
Animals
DNA Damage
Endothelial Cells
Female
Gene Expression Profiling
Gene Expression Regulation, Developmental
Heterochromatin
High-Throughput Nucleotide Sequencing
Hippocampus
Humans
Inflammation
Long Interspersed Nucleotide Elements
Macaca mulatta
Male
Microglia
Nerve Tissue Proteins
Neural Stem Cells
Neurogenesis
Neurons
Oligodendroglia
Single-Cell Analysis
Transcriptome

Authors

Zhang, Hui
Li, Jiaming
Ren, Jie
Sun, Shuhui
Ma, Shuai
Zhang, Weiqi
Yu, Yang
Cai, Yusheng
Yan, Kaowen
Li, Wei
Hu, Baoyang
Chan, Piu
Zhao, Guo-Guang
Belmonte, Juan Carlos Izpisua
Zhou, Qi
Qu, Jing
Wang, Si
Liu, Guang-Hui

Recommend literature





Similar data