STEP: profiling cellular-specific targets and pathways of bioactive small molecules in tissues via integrating single-cell transcriptomics and chemoproteomics

Chen, Jiayun1,2; Chu, Zheng1,2; Zhang, Qian3,4; Wang, Chen1,2; Luo, Piao3,4; Zhang, Ying1,2; Xia, Fei1,2; Gu, Liwei1,2; Wong, Yin Kwan5; Shi, Qiaoli1,2; Xu, Chengchao1,2; Tang, Huan1,2; Wang, Jigang1,2,3,4,5,6

2024-03-20

10.1039/d3sc04826h

CHEMICAL SCIENCE   影响因子和分区

2041-6520

2041-6539

Identifying the cellular targets of bioactive small molecules within tissues has been a major concern in drug discovery and chemical biology research. Compared to cell line models, tissues consist of multiple cell types and complicated microenvironments. Therefore, elucidating the distribution and heterogeneity of targets across various cells in tissues would enhance the mechanistic understanding of drug or toxin action in real-life scenarios. Here, we present a novel multi-omics integration pipeline called Single-cell TargEt Profiling (STEP) that enables the global profiling of protein targets in mammalian tissues with single-cell resolution. This pipeline integrates single-cell transcriptome datasets with tissue-level protein target profiling using chemoproteomics. Taking well-established classic drugs such as aspirin, aristolochic acid, and cisplatin as examples, we confirmed the specificity and precision of cellular drug-target profiles and their associated molecular pathways in tissues using the STEP analysis. Our findings provide more informative insights into the action modes of bioactive molecules compared to in vitro models. Collectively, STEP represents a novel strategy for profiling cellular-specific targets and functional processes with unprecedented resolution.

SCI ; EI

英语

通讯

National Key Research and Development Program of China["CI2023D003","CI2023E002"] ; Scientific and Technological Innovation Project of the China Academy of Chinese Medical Sciences["2020YFA0908000","2022YFC2303603"] ; National Key Research and Development Program of China[ZYYCXTD-C-202002] ; Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine[JCYJ20210324115800001] ; Science and Technology Foundation of Shenzhen["32201177","82141001","82074098"] ; National Natural Science Foundation of China["CI2021A05101","CI2021A05104"] ; Science and Technology Foundation of Shenzhen (Shenzhen Clinical Medical Research Center for Geriatric Diseases)[B2302051] ; Shenzhen Medical Research Fund["ZZ14-YQ-061","ZZ16-ND-10-24","ZZ14-FL-002"]

Chemistry

Chemistry, Multidisciplinary

WOS:001179852500001

ROYAL SOC CHEMISTRY

Web of Science

1.Inst Chinese Mat Med, Artemisinin Res Ctr, State Key Lab Qual Ensurance & Sustainable Use Dao, Beijing 100700, Peoples R China
2.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing 100700, Peoples R China
3.Southern Med Univ, Sch Tradit Chinese Med Sci, Guangzhou 510515, Peoples R China
4.Southern Med Univ, Sch Pharmaceut Sci, Guangzhou 510515, Peoples R China
5.Southern Univ Sci & Technol, Shenzhen Peoples Hosp, Affiliated Hosp 1, Dept Nephrol,Shenzhen Key Lab Kidney Dis,Shenzhen, Shenzhen 518020, Peoples R China
6.Henan Univ, Sch Pharm, State Key Lab Antiviral Drugs, Kaifeng 475004, Peoples R China

Chen, Jiayun,Chu, Zheng,Zhang, Qian,et al. STEP: profiling cellular-specific targets and pathways of bioactive small molecules in tissues via integrating single-cell transcriptomics and chemoproteomics[J]. CHEMICAL SCIENCE,2024,15(12).

Chen, Jiayun.,Chu, Zheng.,Zhang, Qian.,Wang, Chen.,Luo, Piao.,...&Wang, Jigang.(2024).STEP: profiling cellular-specific targets and pathways of bioactive small molecules in tissues via integrating single-cell transcriptomics and chemoproteomics.CHEMICAL SCIENCE,15(12).

Chen, Jiayun,et al."STEP: profiling cellular-specific targets and pathways of bioactive small molecules in tissues via integrating single-cell transcriptomics and chemoproteomics".CHEMICAL SCIENCE 15.12(2024).