2. Academic Validation
  3. Single-cell EpiChem jointly measures drug-chromatin binding and multimodal epigenome

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

  • Nat Methods. 2024 Jul 18. doi: 10.1038/s41592-024-02360-0.
Chao Dong # 1,  Xiaoxuan Meng # 1,  Tong Zhang # 1,  Zhifang Guo # 2 3 4,  Yaxi Liu 1,  Peihuang Wu 2,  Shiwei Chen 3 4,  Fanqi Zhou 5,  Yanni Ma 5,  Haiqing Xiong 6 7,  Shaokun Shu 8 9 10,  Aibin He 11 12 13
Affiliations

Affiliations

  • 1 Institute of Molecular Medicine, National Biomedical Imaging Center, College of Future Technology, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China.
  • 2 State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China.
  • 3 Peking University International Cancer Institute, Beijing, China.
  • 4 Peking University-Yunnan Baiyao International Medical Research Center, Beijing, China.
  • 5 State Key Laboratory of Medical Molecular Biology, Haihe laboratory of Cell Ecosystem, Key Laboratory of RNA and Hematopoietic Regulation, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China.
  • 6 State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, China.
  • 7 Tianjin Institutes of Health Science, Tianjin, China.
  • 8 State Key Laboratory of Molecular Oncology, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Lymphoma, Peking University Cancer Hospital & Institute, Beijing, China. shaokun_shu@bjmu.edu.cn.
  • 9 Peking University International Cancer Institute, Beijing, China. shaokun_shu@bjmu.edu.cn.
  • 10 Peking University-Yunnan Baiyao International Medical Research Center, Beijing, China. shaokun_shu@bjmu.edu.cn.
  • 11 Institute of Molecular Medicine, National Biomedical Imaging Center, College of Future Technology, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, China. ahe@pku.edu.cn.
  • 12 Key laboratory of Carcinogenesis and Translational Research of Ministry of Education of China, Peking University Cancer Hospital & Institute, Beijing, China. ahe@pku.edu.cn.
  • 13 Peking University Chengdu Academy for Advanced Interdisciplinary Biotechnologies, Chengdu, China. ahe@pku.edu.cn.
  • # Contributed equally.
PMID: 39025969 DOI: 10.1038/s41592-024-02360-0
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.

Figures
Products