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Cross-Species Insights from Single-Nucleus Sequencing Highlight Aging-Related Hippocampal Features in Tree Shrew

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机构: [1]Department of Neurosurgery, Institute of Neurological Disease, National-Local Joint Engineering Research Center of Translational Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. [2]Department of Anesthesiology, The First People's Hospital of Zunyi (The Third Affiliated Hospital of Zunyi Medical University), Zunyi 563000, Guizhou, China. [3]Translational Neuromedicine Laboratory, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou, China. [4]Science and Education Department, Mental Health Center of Kunming Medical University, Kunming 650034, Yunnan, China. [5]Institute of Neuroscience, Kunming Medical University, Kunming 650500, Yunnan, China. [6]State Key Lab of Biotherapy, Sichuan University, Chengdu 610041, Sichuan, China.
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关键词: tree shrew cross-species aging neural stem cells single-nucleus RNA sequencing

摘要:
The tree shrew brain has garnered considerable attention due to its remarkable similarities to human brain. However, the cellular composition and genetic signatures of tree shrew hippocampus across postnatal life remain poorly characterized. Here, we establish the first single-nucleus transcriptomic atlas of tree shrew hippocampus spanning postnatal life, detailing the dynamics and diversity of the neurogenic lineage, oligodendrocytes, microglia, and endothelial cells. Notably, cross-species transcriptomic comparison among humans, macaques, tree shrews, and mice reveals that the tree shrew transcriptome resembles that of macaques, making it a promising model for simulating human neurological diseases. More interestingly, we identified a unique class of tree shrew-specific neural stem cells and established SOX6, ADAMTS19, and MAP2 as their markers. Furthermore, aberrant gene expression and cellular dysfunction in the tree shrew hippocampus are linked to neuroinflammation and cognitive impairment during tree shrew aging. Our study provides extensive resources on cell composition and transcriptomic profiles, serving as a foundation for future research on neurodevelopmental and neurological disorders in tree shrews.© The Author(s) 2025. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution.

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大类 | 1 区 生物学
小类 | 1 区 遗传学 2 区 生化与分子生物学 2 区 进化生物学
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第一作者机构: [1]Department of Neurosurgery, Institute of Neurological Disease, National-Local Joint Engineering Research Center of Translational Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. [2]Department of Anesthesiology, The First People's Hospital of Zunyi (The Third Affiliated Hospital of Zunyi Medical University), Zunyi 563000, Guizhou, China. [3]Translational Neuromedicine Laboratory, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou, China.
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通讯机构: [1]Department of Neurosurgery, Institute of Neurological Disease, National-Local Joint Engineering Research Center of Translational Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China. [2]Department of Anesthesiology, The First People's Hospital of Zunyi (The Third Affiliated Hospital of Zunyi Medical University), Zunyi 563000, Guizhou, China. [3]Translational Neuromedicine Laboratory, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou, China.
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