北京大学何爱彬、北京大学肿瘤医院舒绍坤研究小组近日取得一项新成果。他们利用单细胞EpiChem联合测量药物-染色质结合和多模态表观基因组。该项研究成果发表在2024年7月18日出版的《自然—方法学》上。

课题组人员提出利用EpiChem原位单细胞联合绘制绘小分子和多模态表观基因组图谱。该团队展示了人类结直肠癌(CRC)类器官中三种小分子与组蛋白修饰、染色质可及性或靶蛋白的单细胞联合分析。综合多模态分析揭示了在异质性人类结直肠癌类器官中，染色质状态的不同药物相互作用。

该团队进一步揭示了小分子药物治疗后人类结直肠癌类器官中，不同细胞类型的药物基因组结合动力学和适应性表观基因组。这种方法提供了一种独特的工具，来开发细胞类型特异性药物作用的机制。

据了解，研究小分子抑制剂在癌症治疗中的分子和细胞功能，通过靶向基因组和表观基因组相关蛋白来激发作用，需要在单细胞分辨率下测量药物靶向作用。

附：英文原文

Title: Single-cell EpiChem jointly measures drug–chromatin binding and multimodal epigenome

Author: Dong, Chao, Meng, Xiaoxuan, Zhang, Tong, Guo, Zhifang, Liu, Yaxi, Wu, Peihuang, Chen, Shiwei, Zhou, Fanqi, Ma, Yanni, Xiong, Haiqing, Shu, Shaokun, He, Aibin

Issue&Volume: 2024-07-18

Abstract: Studies of molecular and cellular functions of small-molecule inhibitors in cancer treatment, eliciting effects by targeting genome and epigenome associated proteins, requires measurement of drug-target engagement in single-cell resolution. Here we present EpiChem for in situ single-cell joint mapping of small molecules and multimodal epigenomic landscape. We demonstrate single-cell co-assays of three small molecules together with histone modifications, chromatin accessibility or target proteins in human colorectal cancer (CRC) organoids. Integrated multimodal analysis reveals diverse drug interactions in the context of chromatin states within heterogeneous CRC organoids. We further reveal drug genomic binding dynamics and adaptive epigenome across cell types after small-molecule drug treatment in CRC organoids. This method provides a unique tool to exploit the mechanisms of cell type-specific drug actions.

DOI: 10.1038/s41592-024-02360-0

Source: https://www.nature.com/articles/s41592-024-02360-0