Regional and aging-specific cellular architecture of non-human primate brains
Abstract 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...
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2025-04-01
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| Online Access: | https://doi.org/10.1186/s13073-025-01469-x |
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| author | Yun-Mei Wang Wen-Chao Wang Yongzhang Pan Lin Zeng Jing Wu Zheng-Bo Wang Xiao-Lin Zhuang Ming-Li Li David N. Cooper Sheng Wang Yong Shao Li-Min Wang Ying-Yin Fan Yonghan He Xin-Tian Hu Dong-Dong Wu |
| author_facet | Yun-Mei Wang Wen-Chao Wang Yongzhang Pan Lin Zeng Jing Wu Zheng-Bo Wang Xiao-Lin Zhuang Ming-Li Li David N. Cooper Sheng Wang Yong Shao Li-Min Wang Ying-Yin Fan Yonghan He Xin-Tian Hu Dong-Dong Wu |
| author_sort | Yun-Mei Wang |
| collection | DOAJ |
| description | Abstract 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 knowledge of primate brain organization and highlight the potential involvement of specific molecular and cellular components in both the regionalization and functional integrity of the brain. Our analysis also disclosed extensive transcriptional alterations and cell–cell connections across brain regions in the aging macaques. Finally, by examining the heritability enrichment of human complex traits and diseases, we determined that neurological traits were significantly enriched in neuronal cells and multiple regions with aging-relevant gene expression signatures, while immune-related traits exhibited pronounced enrichment in microglia. Conclusions Taken together, our study presents a valuable resource for investigating the cellular and molecular architecture of the primate nervous system, thereby expanding our understanding of the mechanisms underlying brain function, aging, and disease. |
| format | Article |
| id | doaj-art-8305f2224cb845beba1e4b14f5d1fc05 |
| institution | DOAJ |
| issn | 1756-994X |
| language | English |
| publishDate | 2025-04-01 |
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| series | Genome Medicine |
| spelling | doaj-art-8305f2224cb845beba1e4b14f5d1fc052025-08-20T02:55:35ZengBMCGenome Medicine1756-994X2025-04-0117112710.1186/s13073-025-01469-xRegional and aging-specific cellular architecture of non-human primate brainsYun-Mei Wang0Wen-Chao Wang1Yongzhang Pan2Lin Zeng3Jing Wu4Zheng-Bo Wang5Xiao-Lin Zhuang6Ming-Li Li7David N. Cooper8Sheng Wang9Yong Shao10Li-Min Wang11Ying-Yin Fan12Yonghan He13Xin-Tian Hu14Dong-Dong Wu15State Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Yunnan Key Laboratory of Primate Biomedical ResearchState Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of SciencesInstitute of Medical Genetics, School of Medicine, Cardiff UniversityState Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of SciencesState Key Laboratory of Genetic Evolution & Animal Models, Kunming Institute of Zoology, Chinese Academy of SciencesAbstract 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 knowledge of primate brain organization and highlight the potential involvement of specific molecular and cellular components in both the regionalization and functional integrity of the brain. Our analysis also disclosed extensive transcriptional alterations and cell–cell connections across brain regions in the aging macaques. Finally, by examining the heritability enrichment of human complex traits and diseases, we determined that neurological traits were significantly enriched in neuronal cells and multiple regions with aging-relevant gene expression signatures, while immune-related traits exhibited pronounced enrichment in microglia. Conclusions Taken together, our study presents a valuable resource for investigating the cellular and molecular architecture of the primate nervous system, thereby expanding our understanding of the mechanisms underlying brain function, aging, and disease.https://doi.org/10.1186/s13073-025-01469-xBrainNon-human primateAgingSnRNA-seq |
| spellingShingle | Yun-Mei Wang Wen-Chao Wang Yongzhang Pan Lin Zeng Jing Wu Zheng-Bo Wang Xiao-Lin Zhuang Ming-Li Li David N. Cooper Sheng Wang Yong Shao Li-Min Wang Ying-Yin Fan Yonghan He Xin-Tian Hu Dong-Dong Wu Regional and aging-specific cellular architecture of non-human primate brains Genome Medicine Brain Non-human primate Aging SnRNA-seq |
| title | Regional and aging-specific cellular architecture of non-human primate brains |
| title_full | Regional and aging-specific cellular architecture of non-human primate brains |
| title_fullStr | Regional and aging-specific cellular architecture of non-human primate brains |
| title_full_unstemmed | Regional and aging-specific cellular architecture of non-human primate brains |
| title_short | Regional and aging-specific cellular architecture of non-human primate brains |
| title_sort | regional and aging specific cellular architecture of non human primate brains |
| topic | Brain Non-human primate Aging SnRNA-seq |
| url | https://doi.org/10.1186/s13073-025-01469-x |
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