文献类型：期刊文献

英文题名：Integrative single-cell metabolomics and phenotypic profiling reveals metabolic heterogeneity of cellular oxidation and senescence

作者：Wang, Ziyi[1];Ge, Siyuan[1];Liao, Tiepeng[1];Yuan, Man[1];Qian, Wenwei[1];Chen, Qi[1];Liang, Wei[1];Cheng, Xiawei[2];Zhou, Qinghua[3];Ju, Zhenyu[3];Zhu, Hongying[1,4,5,6];Xiong, Wei[1,4,5,6]

机构：[1]Univ Sci & Technol China, Affiliated Hosp USTC 1, Dept Neurol, Div Life Sci & Med, Hefei 230001, Peoples R China;[2]East China Univ Sci & Technol, Optogenet & Synthet Biol Interdisciplinary Res Ctr, Sch Pharm, Shanghai 200237, Peoples R China;[3]Jinan Univ, Inst Aging Regenerat Med, Coll Life Sci & Technol,Minist Educ, Dept Dev & Regenerat Med,Key Lab Regenerat Med, Guangzhou 510632, Guangdong, Peoples R China;[4]Inst Artificial Intelligence, Hefei Comprehens Natl Sci Ctr, Anhui Prov Key Lab Biomed Imaging & Intelligent Pr, Hefei 230088, Peoples R China;[5]CAS Key Lab Brain Funct & Dis, Hefei 230026, Peoples R China;[6]Anhui Prov Key Lab Biomed Aging Res, Hefei 230026, Peoples R China

年份：2025

卷号：16

期号：1

外文期刊名：NATURE COMMUNICATIONS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:001449678800018)】；

基金：The authors thank Professor Quan Wen (University of Science and Technology of China) for providing the N2 C. elegans strain. We thank Professor Chunlei Cang (University of Science and Technology of China) for providing MEFs. This study was supported by National Key R&D Program of China (2021YFA0804900, 2020YFA0112203), National Natural Science Foundation of China (Grants 32225020, 32430045, 92049304, 32121002 to W.X., 32322033, 32471080, 21974130 and 91849116 to H.Z.), the Strategic Priority Research Program of the Chinese Academy of Sciences (Grant XDB39050000 to W.X.), Key Research Program of Frontier Science (CAS, Grant No. ZDBS-LY-SM002 to W.X.), CAS Interdisciplinary Innovation Team (JCTD-2018-20 to W.X.), the Youth Innovation Promotion Association CAS, the Fundamental Research Funds for the Central Universities, USTC Research Funds of the Double First-Class Initiative (YD9100002001 to W.X. and YD9100002005 to H.Z.), Research Funds of Center for Advanced Interdisciplinary Science and Biomedicine of IHM (QYZD20230011 to W.X.), CAS Project for Young Scientists in Basic Research (YSBR-013 to W.X.), Anhui Provincial Major Science and Technology Project (Grant 202303a07020005 to W.X.), University Synergy Innovation Program of Anhui Province (Grant number GXXT-2022-033 to H.Z.).

语种：英文

摘要：Emerging evidence has unveiled heterogeneity in phenotypic and transcriptional alterations at the single-cell level during oxidative stress and senescence. Despite the pivotal roles of cellular metabolism, a comprehensive elucidation of metabolomic heterogeneity in cells and its connection with cellular oxidative and senescent status remains elusive. By integrating single-cell live imaging with mass spectrometry (SCLIMS), we establish a cross-modality technique capturing both metabolome and oxidative level in individual cells. The SCLIMS demonstrates substantial metabolomic heterogeneity among cells with diverse oxidative levels. Furthermore, the single-cell metabolome predicted heterogeneous states of cells. Remarkably, the pre-existing metabolomic heterogeneity determines the divergent cellular fate upon oxidative insult. Supplementation of key metabolites screened by SCLIMS resulted in a reduction in cellular oxidative levels and an extension of C. elegans lifespan. Altogether, SCLIMS represents a potent tool for integrative metabolomics and phenotypic profiling at the single-cell level, offering innovative approaches to investigate metabolic heterogeneity in cellular processes.