埃默里大学金鹏课题组与芝加哥大学陈梦洁课题组发现，人脑多区域m⁶A表转录组分析揭示了疾病相关位点的时空变化和富集。2025年12月9日出版的《自然—神经科学》杂志发表了这项成果。

该团队在25名年龄从0岁到71岁的不同个体中分析了人脑5个区域（Brodmann区9和24，以及尾状体、海马和丘脑）中m⁶A mRNA的修饰。课题组研究人员发现大脑中m⁶A模式存在广泛的区域差异，尤其是在疾病风险基因中，而与年龄相关的变化在前额皮质中最为突出。将m⁶A数据与全基因组测序相结合，发现m⁶A修饰与疾病相关的遗传位点相关。他们的工作确定了m⁶A修饰的空间和时间变化，并提出了它们如何导致神经系统疾病。

据悉，N⁶ -甲基腺苷（m⁶A）是大脑中主要的RNA修饰，调节神经过程并参与疾病机制。尽管它很重要，但人类大脑中区域性、年龄特异性和性别特异性的m⁶A模式仍然很少被描述。

附：英文原文

Title: Multi-region m6A epitranscriptome profiling of the human brain reveals spatial and temporal variation and enrichment of disease-associated loci

Author: Shafik, Andrew M., Peng, Yong, Zhang, Zijie, Chang, Chen, Wang, Pingluan, Lim, Junghwa, Song, Hongjun, He, Chuan, Chen, Mengjie, Jin, Peng

Issue&Volume: 2025-12-09

Abstract: N6-methyladenosine (m6A) is a major RNA modification in the brain, regulating neural processes and contributing to disease mechanisms. Despite its importance, regional, age-specific and sex-specific m6A patterns in the human brain are still poorly described. Here, we profiled m6A mRNA modifications in five human brain regions (Brodmann areas 9 and 24, and the caudate, hippocampus and thalamus) across 25 individuals of different ages, ranging from 0 to 71 years old. We uncovered widespread regional differences for m6A patterns in the brain, notably in disease-risk genes, while age-related changes were most prominent in the prefrontal cortex. Integrating m6A data with whole-genome sequencing revealed that m6A modifications are associated with disease-related genetic loci. Our work identifies the spatial and temporal variation in m6A modifications and suggests how they could contribute to neurological disorders.

DOI: 10.1038/s41593-025-02112-z

Source: https://www.nature.com/articles/s41593-025-02112-z