Open AccessSingle‐cell analysis reveals transcriptomic reprogramming in aging primate entorhinal cortex and the relevance with Alzheimer's disease
Author(s) -
Li MingLi,
Wu ShiHao,
Song Bo,
Yang Jing,
Fan LiYuan,
Yang Yang,
Wang YunChao,
Yang JingHua,
Xu Yuming
Publication year - 2022
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13723
Subject(s) - reprogramming , biology , entorhinal cortex , disease , alzheimer's disease , relevance (law) , neuroscience , transcriptome , computational biology , cell , genetics , hippocampus , gene , gene expression , medicine , political science , law
The entorhinal cortex is of great importance in cognition and memory, its dysfunction causes a variety of neurological diseases, particularly Alzheimer's disease (AD). Yet so far, research on entorhinal cortex is still limited. Here, we provided the first single‐nucleus transcriptomic map of primate entorhinal cortex aging. Our result revealed that synapse signaling, neurogenesis, cellular homeostasis, and inflammation‐related genes and pathways changed in a cell‐type‐specific manner with age. Moreover, among the 7 identified cell types, we highlighted the neuronal lineage that was most affected by aging. By integrating multiple datasets, we found entorhinal cortex aging was closely related to multiple neurodegenerative diseases, particularly for AD. The expression levels of APP and MAPT , which generate β‐amyloid (Aβ) and neurofibrillary tangles, respectively, were increased in most aged entorhinal cortex cell types. In addition, we found that neuronal lineage in the aged entorhinal cortex is more prone to AD and identified a subpopulation of excitatory neurons that are most highly associated with AD. Altogether, this study provides a comprehensive cellular and molecular atlas of the primate entorhinal cortex at single‐cell resolution and provides new insights into potential therapeutic targets against age‐related neurodegenerative diseases.