近日，北京大学邢栋团队的论文发现了通过单细胞四组学测序剖析基因调控景观。2026年4月1日出版的《自然》发表了这项成果。

为了全面了解这些调节模式如何汇聚形成细胞身份，研究小组开发了一种单细胞组学测序方法，可以在同一细胞内平行分析基因组构象、组蛋白修饰、染色质可及性和基因表达（CHARM）。将CHARM应用于多主题胚胎干细胞和皮质组织，该研究组重建了完整的表观基因组图谱，揭示了染色质可及性和组蛋白修饰的不同细胞周期动力学，以及调控元件在三维核空间中的空间聚类。利用可解释的机器学习模型，研究团队进一步以高精度确定了以细胞类型和亚型特异性方式调节基因表达的增强子-启动子连接的需求。总之，CHARM能够在单细胞分辨率下对三维表观基因组进行综合解剖，为解码复杂组织中不同细胞的调控景观提供了一个通用平台。

据悉，细胞多样性不仅受到转录组的控制，还受到多层表观基因组调控的控制，包括核小体占用、染色质状态和基因组结构。

附：英文原文

Title: Gene regulatory landscape dissected by single-cell four-omics sequencing

Author: Chen, Yujie, Liu, Zhiyuan, Xu, Heming, Liu, Jiayu, Wang, Mengxuan, Chi, Yi, Liang, Boyuan, Liu, Menghan, Peng, Yongli, Ge, Hao, Xing, Dong

Issue&Volume: 2026-04-01

Abstract: Cellular diversity is governed not only by the transcriptome but also by multiple layers of epigenomic regulation, including nucleosome occupancy, chromatin states and genome architecture1,2,3. Here, to comprehensively understand how these regulatory modalities converge to shape cellular identity, we developed a single-cell four-omics sequencing method that enables parallel profiling of genome conformation, histone modifications, chromatin accessibility and gene expression within the same cell (CHARM). Applying CHARM to mouse embryonic stem cells and cortical tissues, we reconstructed integrated epigenome profiles, uncovering distinct cell-cycle dynamics of chromatin accessibility and histone modification, and spatial clustering of regulatory elements in three-dimensional nuclear space. Leveraging an interpretable machine learning model, we further identified thousands of enhancer–promoter linkages with high accuracy that modulate gene expression in a cell-type- and subtype-specific manner. Together, CHARM enables integrative dissection of the three-dimensional epigenome at single-cell resolution, providing a versatile platform for decoding the regulatory landscape across diverse cells in complex tissues.

DOI: 10.1038/s41586-026-10322-z

Source: https://www.nature.com/articles/s41586-026-10322-z