美国杜克大学Kate D. Meyer研究组发现，小鼠大脑中的单细胞m⁶A分析揭示，细胞类型特异的RNA甲基组和与年龄相关的差异甲基化。相关论文于2024年9月24日发表在《自然—神经科学》杂志上。

研究人员开发了一种小鼠模型，可以在感兴趣的任何组织中以单细胞分辨率进行转录组范围的N⁶-甲基腺苷（m⁶A）检测。研究人员使用这些小鼠在不同脑区及小鼠皮层的单细胞中绘制m⁶A分布，发现脑区和细胞类型之间存在高度共享的甲基化。

然而，研究人员也识别出在神经元中编码重要神经信号调节因子的少量差异甲基化mRNA，并发现小胶质细胞的m⁶A水平低于其他细胞类型。最后，研究人员在老年小鼠中进行了单细胞m⁶A绘制，并识别出许多具有年龄依赖性变化的转录本。

据介绍，m⁶A是大脑中一种丰富的mRNA修饰，对神经发育和大脑功能具有重要作用。然而，由于技术限制，尚无法在构成大脑的各个细胞类型中进行m⁶A位点的全局分析。

附：英文原文

Title: Single-cell m6A profiling in the mouse brain uncovers cell type-specific RNA methylomes and age-dependent differential methylation

Author: Tegowski, Matthew, Prater, Anna K., Holley, Christopher L., Meyer, Kate D.

Issue&Volume: 2024-09-24

Abstract: N6-methyladenosine (m6A) is an abundant mRNA modification in the brain that has important roles in neurodevelopment and brain function. However, because of technical limitations, global profiling of m6A sites within the individual cell types that make up the brain has not been possible. Here, we develop a mouse model that enables transcriptome-wide m6A detection in any tissue of interest at single-cell resolution. We use these mice to map m6A across different brain regions and within single cells of the mouse cortex and discover a high degree of shared methylation across brain regions and cell types. However, we also identify a small number of differentially methylated mRNAs in neurons that encode important regulators of neuronal signaling, and we discover that microglia have lower levels of m6A than other cell types. Finally, we perform single-cell m6A mapping in aged mice and identify many transcripts with age-dependent changes in m6A.

DOI: 10.1038/s41593-024-01768-3

Source: https://www.nature.com/articles/s41593-024-01768-3