Spatial transcriptomics reveals laminar and cell-type-specific A-to-I RNA editing signatures in the macaque cortex

ADAR-mediated A-to-I RNA editing is crucial for proper neuronal function. However, its spatial signatures in the cerebral cortex remain largely unexplored. To address this, we developed SRDRE, an analysis framework for identifying RNA editing sites in spatial transcriptomics data.

By analyzing over 40 million cells across 142 spatially annotated cortical regions in the adult macaque cortex, we uncovered laminar and cell-type-specific RNA editing landscapes. Notably, neuronal RNA editing levels correlated with cortical hierarchy in the visual and somatosensory systems. Parvalbumin neurons exhibited the highest editing activity in most regions.

Furthermore, we identified primate-enriched sites within ion channel genes, specifically in excitatory neuronal subtypes of the prefrontal cortex. Finally, in a preliminary exploratory analysis, we observed altered RNA editing in deeper layers of the dorsolateral prefrontal cortex in macaques exhibiting depressive-like behaviors, suggesting a potential link that warrants further investigation. These findings underscore the role of RNA editing and its potential contributions to cortical specialization, brain evolution, and neuropsychiatric disorders.

We are grateful to Professor Cai Song for her insightful comments. We sincerely thank the China National GeneBank for providing technical support. The project was supported by National Key R&D Program of China (2024YFC3505100), National Natural Science Foundation of China (No. 32571341), National Key R&D Program of China (2022YEF0203200, 2022YFC3400400, 2021YFA0805100, and 2020YFE0205900), National Science and Technology Innovation 2030 Major Program (STI2030-2022ZD0211700, STI2030-2022ZD0205000 and STI2030-2021ZD0200100), Zhejiang Province ‘Vanguard’ R&D Program (2023C03SA103409), and Hangzhou Leading Innovation Team Project.

These authors contributed equally: Cheng Chen, Jing Yang. College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China Cheng Chen, Ziyu Wang, Yunqi Huang & Yong Hou State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Shenzhen, China Cheng Chen, Lingjun Ding, Qiye Li, Ying Lei & Jinrong Huang Cheng Chen, Jing Yang, Zhiyong Zhu, Ziyu Wang, Yunqi Huang, Lingjun Ding, Shiping Liu, Ying Lei & Jinrong Huang Department of Hepatology, The Fourth Clinical Medical College of Guangzhou University of Traditional Chinese Medicine, Shenzhen, China College of Wildlife and Protected Area, Northeast Forestry University, Harbin, China Key Laboratory of Spatial Omics of Zhejiang Province, BGI Research, Hangzhou, China Shanxi Medical University - BGI Collaborative Center for Future Medicine, Shanxi Medical University, Taiyuan, China Correspondence to Ying Lei or Jinrong Huang. The authors declare no competing interests.

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