Regional and aging-specific cellular architecture of non-human primate brains

作者：Yun-Mei Wang, Wenchao Wang, Yongzhang Pan, Lin Zeng, Kaichun Wu, Zhengbo Wang, Xiao-Lin Zhuang, Mingli Li, D.N. Cooper, Sheng Wang, Yong Shao, Limin Wang, Ying-Yin Fan, Yonghan He, Xintian Hu, Dong‐Dong Wu · 发表于：Genome Medicine · 年份：2025 · DOI：10.1186/s13073-025-01469-x · 被引用次数：9 · 研究领域：Single-cell and spatial transcriptomics、Barrier Structure and Function Studies、Neuroinflammation and Neurodegeneration Mechanisms

BACKGROUND: Deciphering the functionality and dynamics of brain networks across different regions and age groups in non-human primates (NHPs) is crucial for understanding the evolution of human cognition as well as the processes underlying brain pathogenesis. However, systemic delineation of the cellular composition and molecular connections among multiple brain regions and their alterations induced by aging in NHPs remain largely unresolved. METHODS: In this study, we performed single-nucleus RNA sequencing on 39 samples collected from 10 brain regions of two young and two aged rhesus macaques using the DNBelab C4 system. Validation of protein expression of signatures specific to particular cell types, brain regions, and aging was conducted through a series of immunofluorescence and immunohistochemistry staining experiments. Loss-of-function experiments mediated by short hairpin RNA (shRNA) targeting two age-related genes (i.e., VSNL1 and HPCAL4) were performed in U251 glioma cells to verify their aging effects. Senescence-associated beta-galactosidase (SA-β-gal) staining and quantitative PCR (qPCR) of senescence marker genes were employed to assess cellular senescence in U251 cells. RESULTS: We have established a large-scale cell atlas encompassing over 330,000 cells for the rhesus macaque brain. Our analysis identified numerous gene expression signatures that were specific to particular cell types, subtypes, brain regions, and aging. These datasets greatly expand our knowl...