浙江大学阮一骏研究团队揭示了整个小鼠大脑中三维表观基因组和转录组的三组单细胞图谱。2025年4月29日出版的《自然—方法学》杂志发表了这项成果。

在这里，该研究组报告了一种单细胞方法ChAIR，同时绘制染色质可及性，染色质相互作用和RNA表达。在培养细胞中进行验证后，该课题组人员将ChAIR应用于整个小鼠大脑，并描绘了成熟和衰老过程中表观基因组、三维基因组和转录组的协调动态。特别是，以基因为中心的染色质相互作用和开放染色质状态提供了细胞类型特异性转录的三维表观基因组机制，并揭示了空间分辨的特异性。

重要的是，单个细胞中染色质短距离和超长接触的组成与转录活性、染色质开放状态和基因组折叠密度显著相关。这种基因组特性，以及相关的细胞特性，在不同解剖区域的神经元和非神经元细胞中，在整个生命周期中是不同的，这意味着在脑细胞中起作用的核机械基因组机制是不同的。他们的结果证明了ChAIR在揭示复杂组织中细胞类型特异性转录的单细胞三维表观基因组状态方面的随机性。

研究人员表示，探索转录程序的基因组基础一直是他们长期以来的研究重点。

附：英文原文

Title: Tri-omic single-cell mapping of the 3D epigenome and transcriptome in whole mouse brains throughout the lifespan

Author: Chai, Haoxi, Huang, Xingyu, Xiong, Guangzhou, Huang, Jiaxiang, Pels, Katarzyna Karolina, Meng, Lingyun, Han, Jin, Tang, Dongmei, Pan, Guanjing, Deng, Liang, Xiao, Qin, Wang, Xiaotao, Zhang, Meng, Banecki, Krzysztof, Plewczynski, Dariusz, Wei, Chia-Lin, Ruan, Yijun

Issue&Volume: 2025-04-29

Abstract: Exploring the genomic basis of transcriptional programs has been a long-standing research focus. Here we report a single-cell method, ChAIR, to map chromatin accessibility, chromatin interactions and RNA expression simultaneously. After validating in cultured cells, we applied ChAIR to whole mouse brains and delineated the concerted dynamics of epigenome, three-dimensional (3D) genome and transcriptome during maturation and aging. In particular, gene-centric chromatin interactions and open chromatin states provided 3D epigenomic mechanism underlying cell-type-specific transcription and revealed spatially resolved specificity. Importantly, the composition of short-range and ultralong chromatin contacts in individual cells is remarkably correlated with transcriptional activity, open chromatin state and genome folding density. This genomic property, along with associated cellular properties, differs in neurons and non-neuronal cells across different anatomic regions throughout the lifespan, implying divergent nuclear mechano-genomic mechanisms at play in brain cells. Our results demonstrate ChAIR’s robustness in revealing single-cell 3D epigenomic states of cell-type-specific transcription in complex tissues.

DOI: 10.1038/s41592-025-02658-7

Source: https://www.nature.com/articles/s41592-025-02658-7