2. Academic Validation
  3. Integrative single-cell metabolomics and phenotypic profiling reveals metabolic heterogeneity of cellular oxidation and senescence

Integrative single-cell metabolomics and phenotypic profiling reveals metabolic heterogeneity of cellular oxidation and senescence

  • Nat Commun. 2025 Mar 20;16(1):2740. doi: 10.1038/s41467-025-57992-3.
Ziyi Wang 1,  Siyuan Ge 1,  Tiepeng Liao 1,  Man Yuan 1,  Wenwei Qian 1,  Qi Chen 1,  Wei Liang 1,  Xiawei Cheng 2,  Qinghua Zhou 3,  Zhenyu Ju 3,  Hongying Zhu 4 5 6 7,  Wei Xiong 8 9 10 11
Affiliations

Affiliations

  • 1 Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 230001, Hefei, China.
  • 2 School of Pharmacy, Optogenetics & Synthetic Biology Interdisciplinary Research Center, East China University of Science and Technology, 200237, Shanghai, China.
  • 3 Key Laboratory of Regenerative Medicine of Ministry of Education, Institute of Aging and Regenerative Medicine, Department of Developmental & Regenerative Medicine, College of Life Science and Technology, Jinan University, 510632, Guangzhou, Guangdong, China.
  • 4 Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 230001, Hefei, China. zhuhy62@ustc.edu.cn.
  • 5 Anhui Province Key Laboratory of Biomedical Imaging and Intelligent Processing, Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, 230088, Hefei, China. zhuhy62@ustc.edu.cn.
  • 6 CAS Key Laboratory of Brain Function and Disease, 230026, Hefei, China. zhuhy62@ustc.edu.cn.
  • 7 Anhui Province Key Laboratory of Biomedical Aging Research, 230026, Hefei, China. zhuhy62@ustc.edu.cn.
  • 8 Department of Neurology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 230001, Hefei, China. wxiong@ustc.edu.cn.
  • 9 Anhui Province Key Laboratory of Biomedical Imaging and Intelligent Processing, Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, 230088, Hefei, China. wxiong@ustc.edu.cn.
  • 10 CAS Key Laboratory of Brain Function and Disease, 230026, Hefei, China. wxiong@ustc.edu.cn.
  • 11 Anhui Province Key Laboratory of Biomedical Aging Research, 230026, Hefei, China. wxiong@ustc.edu.cn.
PMID: 40113759 DOI: 10.1038/s41467-025-57992-3
Abstract

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.

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