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Nature Methods

Nature Methods

IF: 32.1
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Single-cell EpiChem jointly measures drug–chromatin binding and multimodal epigenome

Published:18 July 2024 DOI: 10.1038/s41592-024-02360-0 PMID: 39025969
Chao Dong, Xiaoxuan Meng, Tong Zhang, Zhifang Guo, Yaxi Liu, Peihuang Wu, Shiwei Chen, Fanqi Zhou, Yanni Ma, Haiqing Xiong, Shaokun Shu, Aibin He

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. EpiChem enables the co-profiling of small molecule–DNA interactions and multiple epigenomic features in single cells.

Substances (16)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Doxorubicin hydrochloride 25316-40-9 C27H29NO11.ClH 956 suppliers $15.00-$7060.00
Doxorubicin hydrochloride 25316-40-9 C27H29NO11.ClH 956 suppliers $15.00-$7060.00
Doxorubicin hydrochloride 25316-40-9 C27H29NO11.ClH 956 suppliers $15.00-$7060.00
Doxorubicin hydrochloride 25316-40-9 C27H29NO11.ClH 956 suppliers $15.00-$7060.00
(+)-JQ-1 1268524-70-4 C23H25ClN4O2S 293 suppliers $9.00-$5000.00
(+)-JQ-1 1268524-70-4 C23H25ClN4O2S 293 suppliers $9.00-$5000.00
(+)-JQ-1 1268524-70-4 C23H25ClN4O2S 293 suppliers $9.00-$5000.00
(+)-JQ-1 1268524-70-4 C23H25ClN4O2S 293 suppliers $9.00-$5000.00
THZ1 1604810-83-4 C31H28ClN7O2 130 suppliers $36.00-$2100.00
THZ1 1604810-83-4 C31H28ClN7O2 130 suppliers $36.00-$2100.00

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