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

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.