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Single-cell signaling network profiling during redox stress reveals dynamic redox regulation in immune cells

Author

Listed:
  • Yi-Chuan Wang

    (National Yang Ming Chiao Tung University
    Academia Sinica)

  • Ping-Hsun Wu

    (Kaohsiung Medical University
    Kaohsiung Medical University
    Kaohsiung Medical University)

  • Wen-Chieh Ting

    (National Taiwan University
    Retain Biotech)

  • Yi-Fu Wang

    (Academia Sinica)

  • Ming-Han Yang

    (Academia Sinica)

  • Tung-Hung Su

    (National Taiwan University Hospital)

  • Jia-Ying Su

    (Academia Sinica)

  • Hsun-I Sun

    (National Taiwan University
    Retain Biotech)

  • Wei-Min Huang

    (Retain Biotech)

  • Pei-Ling Tsai

    (Retain Biotech)

  • Gerlinde Wernig

    (Stanford University School of Medicine)

  • Ping-Chih Ho

    (University of Lausanne
    University of Lausanne)

  • Limei Wang

    (University of Lausanne
    University of Lausanne)

  • Chen-Tu Wu

    (National Taiwan University Hospital and National Taiwan University College of Medicine)

  • Yih-Leong Chang

    (National Taiwan University Hospital and National Taiwan University College of Medicine)

  • Tseng-Cheng Chen

    (National Taiwan University Hospital and National Taiwan University College of Medicine)

  • Tzu-Ching Meng

    (Academia Sinica
    National Taiwan University)

  • Yao-Ming Chang

    (Academia Sinica)

  • Shih-Lei Lai

    (Academia Sinica)

  • Chia-Wei Li

    (Academia Sinica)

  • Tai-Ming Ko

    (Academia Sinica
    National Yang Ming Chiao Tung University)

  • Kai-Chien Yang

    (Academia Sinica
    National Taiwan University Hospital
    National Taiwan University)

  • Ya-Jen Chang

    (Academia Sinica)

  • Yijuang Chern

    (Academia Sinica)

  • Mei-Chuan Kuo

    (Kaohsiung Medical University
    Kaohsiung Medical University)

  • Yen-Tsung Huang

    (Academia Sinica)

  • Yi-Shiuan Tzeng

    (Academia Sinica)

  • Jih-Luh Tang

    (National Taiwan University
    Retain Biotech
    National Taiwan University Hospital)

  • Shih-Yu Chen

    (Academia Sinica)

Abstract

In eukaryotic cells, reactive oxygen species (ROS) serve as crucial signaling components. ROS are potentially toxic, so constant adjustments are needed to maintain cellular health. Here we describe a single-cell, mass cytometry-based method that we call signaling network under redox stress profiling (SN-ROP) to monitor dynamic changes in redox-related pathways during redox stress. SN-ROP quantifies ROS transporters, enzymes, oxidative stress products and associated signaling pathways to provide information on cellular redox regulation. Applied to diverse cell types and conditions, SN-ROP reveals unique redox patterns and dynamics including coordinated shifts in CD8+ T cells upon antigen stimulation as well as variations in CAR-T cell persistence. Furthermore, SN-ROP analysis uncovers environmental factors such as hypoxia and T cell exhaustion for influencing redox balance, and also reveals distinct features in patients on hemodialysis. Our findings thus support the use of SN-ROP to elucidate intricate redox networks and their implications in immune cell function and disease.

Suggested Citation

  • Yi-Chuan Wang & Ping-Hsun Wu & Wen-Chieh Ting & Yi-Fu Wang & Ming-Han Yang & Tung-Hung Su & Jia-Ying Su & Hsun-I Sun & Wei-Min Huang & Pei-Ling Tsai & Gerlinde Wernig & Ping-Chih Ho & Limei Wang & Che, 2025. "Single-cell signaling network profiling during redox stress reveals dynamic redox regulation in immune cells," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-60727-z
    DOI: 10.1038/s41467-025-60727-z
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