Tri-omic mapping revealed concerted dynamics of 3D epigenome and transcriptome in brain cells

作者：Haoxi Chai, Xingyu Huang, Guangzhou Xiong, Jiaxiang Huang, Katarzyna Pels, Lingyun Meng, Jin Han, Dongmei Tang, Guanjing Pan, Liang Deng, Qin Xiao, Xiaotao Wang, Zhang Meng, Krzysztof Banecki, Dariusz Plewczyński, Chia‐Lin Wei, Yijun Ruan · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2024 · DOI：10.1101/2024.05.03.592322 · 被引用次数：6 · 研究领域：Genomics and Chromatin Dynamics、Epigenetics and DNA Methylation、Single-cell and spatial transcriptomics

Abstract Exploring the genomic basis of transcriptional programs has been a longstanding research focus. Here, we report a high-throughput single-cell tri-omic method to capture ch romatin a ccessibility, interaction, and R NA simultaneously (ChAIR). After validating in cultured cells, we applied ChAIR to brain cells across mouse lifespan and delineated the concerted dynamics of 3D-epigenomic architecture and transcription during maturation and aging. Particularly, ultra-long chromatin megacontacts and promoter-associated 3D-epigenomic states are effective in defining cell identity and revealing spatially-resolved anatomic specificity. Importantly, we found that neurons in different brain regions and non-neuronal cells may undergo divergent genomic mechanisms during differentiation and aging. Our results demonstrated ChAIR’s robustness of connecting chromatin folding architecture with cellular property and its potential applications to address complex questions in single-cell resolution and spatial specificity.