Abstract
Utilizing non-human primates to study the role of human Tau and its related pathologies is logical and important due to their closer similarity to human brain structure and function. In our earlier research, we generated a transgenic cynomolgus monkey model expressing Tau (P301L) through lentiviral infection of monkey embryos. These monkeys exhibited age-dependent neurodegeneration and motor dysfunction. Single-nucleus RNA sequencing (snRNA-seq) is a powerful and promising technique for elucidating the cellular complexity and pathology across different tissues. However, single-cell data from non-human primate models of Tau pathology are currently nonexistent. In this study, we performed snRNA-seq on the hippocampus, striatum, and spinal cord of Tau (P301L) monkey, providing the first snRNA-seq atlas of multiple tissue regions in a non-human primate model that simulates human tauopathies. This will offer crucial data references for cross-species single-cell level studies of tau and its related pathologies.
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Data availability
The single-nucleus RNA sequencing (snRNA-seq) data generated in this study have been deposited in the NCBI BioProject database under accession number PRJNA132764. Raw sequencing data and detailed sample descriptions are available via the SRA under accession SRP63104633, and BioSample accessions SAMN51289346–SAMN51289351. Additionally, the fully processed snRNA-seq datasets have been uploaded to the GEO and can be accessed under accession number GSE31717634. The processed gene lists, including differentially expressed genes, cell-type marker genes, and the top 200 signature genes for cross-species DAM-like microglial clusters, have been deposited in Zenodo (https://zenodo.org/records/18612605)35.
Code availability
It is important to note that no specific custom code was employed during the analysis of the current dataset. The analyses and image generation were conducted using the following open-access software programs: Cell Ranger (3.0.1), Scanpy (1.11.3)27, Omicverse (1.7.5)27, ROGUE (1.0)30, and Seurat (5.4.0)39. All analyses were implemented in R (4.4.3) and Python (3.10.13).
References
Zhang, Y., Wu, K.-M., Yang, L., Dong, Q. & Yu, J.-T. Tauopathies: New perspectives and challenges. Mol. Neurodegener. 17, 28 (2022).
Samudra, N., Lane-Donovan, C., VandeVrede, L. & Boxer, A. L. Tau pathology in neurodegenerative disease: Disease mechanisms and therapeutic avenues. J. Clin. Invest. 135 (2023).
Langerscheidt, F. et al. Genetic forms of tauopathies: Inherited causes and implications of alzheimer’s disease-like TAU pathology in primary and secondary tauopathies. J. Neurol. 271, 2992–3018 (2024).
Hallmarks of neurodegenerative diseases. Cell 186, 693–714 (2023).
Samudra, N., Lane-Donovan, C., VandeVrede, L. & Boxer, A. L. Tau pathology in neurodegenerative disease: Disease mechanisms and therapeutic avenues. J. Clin. Invest. 133 (2023).
Targeting tau. Clinical trials and novel therapeutic approaches. Neurosci. Lett. 731, 134919 (2020).
Creekmore, B. C., Watanabe, R. & Lee, E. B. Neurodegenerative disease tauopathies. Annu. Rev. Pathol. 19, 345–370 (2024).
Yoshiyama, Y. et al. Synapse loss and microglial activation precede tangles in a P301S tauopathy mouse model. Neuron 53, 337–351 (2007).
Schweighauser, M. et al. Cryo-EM structures of tau filaments from the brains of mice transgenic for human mutant P301S tau. Acta Neuropathol. Commun. 11, 160 (2023).
Wenger, K. et al. Common mouse models of tauopathy reflect early but not late human disease. Mol. Neurodegener. 18, 10 (2023).
Guo, T., Dakkak, D., Rodriguez-Martin, T., Noble, W. & Hanger, D. P. A pathogenic tau fragment compromises microtubules, disrupts insulin signaling and induces the unfolded protein response. Acta Neuropathol. Commun. 7, 2 (2019).
Polis, B. & Samson, A. O. Addressing the discrepancies between animal models and human alzheimer’s disease pathology: Implications for translational research. J. Alzheimers Dis. 98, 1199–1218 (2024).
He, F. et al. A mass-producible macaque model displays a durable alzheimer-like cognitive deficit and hallmark amyloid-β/tau/neurofilament light chain pathologies. J. Alzheimer’s Dis. 105, 1432–1446 (2025).
Esquerda-Canals, G., Montoliu-Gaya, L., Güell-Bosch, J. & Villegas, S. Mouse models of alzheimer’s disease. J. Alzheimers Dis. JAD 57, 1171–1183 (2017).
Chen, Z.-Y. & Zhang, Y. Animal models of alzheimer’s disease: Applications, evaluation, and perspectives. Zool. Res. 43, 1026–1040 (2022).
Zakaria, R. et al. Lipopolysaccharide-induced memory impairment in rats: A model of alzheimer’s disease. Physiol. Res. 66, 553–565 (2017).
Puzzo, D., Gulisano, W., Palmeri, A. & Arancio, O. Rodent models for alzheimer’s disease drug discovery. Expert Opin. Drug Discov. 10, 703–711 (2015).
Jiang, Z. et al. A nonhuman primate model with alzheimer’s disease-like pathology induced by hippocampal overexpression of human tau. Alzheimers Res. Ther. 16, 22 (2024).
Beckman, D. et al. A novel tau-based rhesus monkey model of alzheimer’s pathogenesis. Alzheimers Dement. J. Alzheimers Assoc. 17, 933–945 (2021).
Tu, Z. et al. Tauopathy promotes spinal cord-dependent production of toxic amyloid-beta in transgenic monkeys. Signal Transduct. Target. Ther. 8, 358 (2023).
Ali, M. et al. Temporal transcriptomic changes in the THY-Tau22 mouse model of tauopathy display cell type- and sex-specific differences. Acta Neuropathol. Commun. 13, 93 (2025).
Kim, D. W. et al. Amyloid-beta and tau pathologies act synergistically to induce novel disease stage-specific microglia subtypes. Mol. Neurodegener. 17, 83 (2022).
Dugger, B. N. et al. The distribution of phosphorylated tau in spinal cords of alzheimer’s disease and non-demented individuals. J. Alzheimers Dis. JAD 34, 529–536 (2013).
Lorenzi, R. M. et al. Unsuspected involvement of spinal cord in alzheimer disease. Front. Cell. Neurosci. 14 (2020).
Xie, Q., Zhao, W.-J., Ou, G.-Y. & Xue, W.-K. An overview of experimental and clinical spinal cord findings in alzheimer’s disease. Brain Sci. 9, 168 (2019).
Zhou, Y. et al. Spinal cord tau pathology induces tactile deficits and cognitive impairment in alzheimer’s disease via dysregulation of CCK neurons. Nat. Neurosci. 1–16, https://doi.org/10.1038/s41593-025-02137-4 (2025).
Wolf, F. A., Angerer, P. & Theis, F. J. SCANPY: Large-scale single-cell gene expression data analysis. Genome Biol. 19, 15 (2018).
Wolock, S. L., Lopez, R. & Klein, A. M. Scrublet: Computational identification of cell doublets in single-cell transcriptomic data. Cell Syst. 8, 281–291.e9 (2019).
Lopez, R., Regier, J., Cole, M. B., Jordan, M. I. & Yosef, N. Deep generative modeling for single-cell transcriptomics. Nat. Methods 15, 1053–1058 (2018).
Liu, B. et al. An entropy-based metric for assessing the purity of single cell populations. Nat. Commun. 11, 3155 (2020).
Zhao, Z. GEO. https://identifiers.org/geo/GSE272082 (2025).
Lee, S., Meilandt, W. J., Friedman, B. A., Bohlen, C. J. & Hansen, D. V. GEO. https://identifiers.org/geo/GSE153895 (2021).
NCBI Sequence Read Archive https://identifiers.org/ncbi/insdc.sra:SRP631046 (2026).
Tu, Z. et al. GEO. https://identifiers.org/geo/GSE317176 (2026).
Han, B., Ouyang, W., Chen, Y., Chen, D., & Liang, W. Single-nucleus RNA sequencing dataset of diverse tissues from wild-type monkey and Tau-P301L transgenic monkey, Zenodo, https://doi.org/10.5281/zenodo.18612605 (2026).
Martins-Ferreira, R. et al. The human microglia atlas (HuMicA) unravels changes in disease-associated microglia subsets across neurodegenerative conditions. Nat. Commun. 16, 739 (2025).
Hüttenrauch, M. et al. Glycoprotein NMB: A novel alzheimer’s disease associated marker expressed in a subset of activated microglia. Acta Neuropathol. Commun. 6, 108 (2018).
Andersen, J. et al. Single-cell transcriptomic landscape of the developing human spinal cord. Nat. Neurosci. 26, 902–914 (2023).
Hao, Y. et al. Dictionary learning for integrative, multimodal and scalable single-cell analysis. Nat. Biotechnol. 42, 293–304 (2024).
Acknowledgements
The author thanks Xiaojiang Li and Shihua Li from Jinan University. This work was supported by the National Key Research and Development Program of China (2021YFA0805300,2021YFA0805200), the National Natural Science Foundation of China (32170981,82171244, 81922026).
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Z.T., S.Y. designed the research. All authors performed the research. B.H. wrote the paper, and Z.T., S.Y. edited the paper. All authors have read and approved the article.
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Han, B., Chen, Y., Ouyang, W. et al. Single-nucleus RNA sequencing dataset of diverse tissues from wild-type monkey and Tau-P301L transgenic monkey. Sci Data (2026). https://doi.org/10.1038/s41597-026-06882-4
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DOI: https://doi.org/10.1038/s41597-026-06882-4
