本期文章：《自然—方法学》：Online/在线发表

一种用于揭示单个细胞内高阶染色质结构的单细胞长读长连接测序方法scNanoHi-C，这一成果由北京大学汤富酬课题组经过不懈努力而取得。这一研究成果发表在2023年8月28日出版的国际学术期刊《自然-方法学》上。

为了揭示哺乳动物基因组中多个调控元件如何在单个细胞内相互作用，研究人员开发了scNanoHi-C，它应用纳米孔长读长测序来探索单个细胞内的全基因组近端高阶染色质结构。研究表明scNanoHi-C可以准确有效地分析染色质3D结构，并在单个细胞中区分结构亚型。该方法还可用于检测基因组变异，包括拷贝数变异和结构变异以及单细胞基因组的从头组装。

研究结果还表明，普遍的高阶染色质结构存在于基因组的活性染色质区域，并在单个细胞内系统地鉴定了增强子与其靶启动子之间的多路相互作用。总之，scNanoHi-C为在单细胞水平研究基因组高阶3D结构提供了新的可能。

据悉，调控基因组元件的高阶三维（3D）组织为基因调控提供了拓扑基础，但尚不清楚哺乳动物基因组中多个调控元件如何在单个细胞内相互作用。

附：英文原文

Title: scNanoHi-C: a single-cell long-read concatemer sequencing method to reveal high-order chromatin structures within individual cells

Author: Li, Wen, Lu, Jiansen, Lu, Ping, Gao, Yun, Bai, Yichen, Chen, Kexuan, Su, Xinjie, Li, Mengyao, Liu, June, Chen, Yijun, Wen, Lu, Tang, Fuchou

Issue&Volume: 2023-08-28

Abstract: The high-order three-dimensional (3D) organization of regulatory genomic elements provides a topological basis for gene regulation, but it remains unclear how multiple regulatory elements across the mammalian genome interact within an individual cell. To address this, herein, we developed scNanoHi-C, which applies Nanopore long-read sequencing to explore genome-wide proximal high-order chromatin contacts within individual cells. We show that scNanoHi-C can reliably and effectively profile 3D chromatin structures and distinguish structure subtypes among individual cells. This method could also be used to detect genomic variations, including copy-number variations and structural variations, as well as to scaffold the de novo assembly of single-cell genomes. Notably, our results suggest that extensive high-order chromatin structures exist in active chromatin regions across the genome, and multiway interactions between enhancers and their target promoters were systematically identified within individual cells. Altogether, scNanoHi-C offers new opportunities to investigate high-order 3D genome structures at the single-cell level.

DOI: 10.1038/s41592-023-01978-w