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Academia Sinica Lab for Cell Dynamics Discovered Ferroptotic Trigger Waves as the Hidden Hand that Carves Life, Research Featured in Nature

Date: 2024-07-18

During embryonic development, cells proliferate rapidly and differentiate to form tissues and organs of multicellular organisms. Paradoxically, since the 19th century, scientists have discovered that these processes that foster the creation of life is often accompanied by large-scale cell death. Why? This is a century-old mystery. Dr. Sheng-hong Chen and his team from the Institute of Molecular Biology's Lab for Cell Dynamics discovered that large-scale cell death occurs through Reactive Oxygen Species (ROS)1-mediated ferroptosis trigger waves, published online in Nature in July 2024.

Academia Sinica held a press conference to reveal the research findings today (July 18th 2024). Academia Sinica’s Vice President Tang K. Tang highlighted the team’s efforts in integrating biological and mathematical methods, utilizing innovative quantitative and systems biology approach to tackle a challenging, long-lasting mystery. They identified the cellular signaling system underlying ferroptotic trigger waves, shedding new insights into organogenesis processes.

Revealing the Mystery Behind the Death of Millions of Cells by Chemical and Genetic Perturbations, Mathematical Modeling, and Computer Simulations

Unlike conventional apoptosis and necrosis, ferroptosis is a recently discovered form of cell death whose biological significance remains largely unexplored. Chen’s team demonstrated the pivotal role of ROS feedback loops2 in driving ferroptosis trigger waves. Chen added, “Unlike localized effects that only influence a few neighboring cells, the ROS-mediated ferroptotic trigger waves can lead to cell death of millions of cells.”

The Hidden Hand that Carves Life: Ferroptotic Trigger Waves

The mechanism of the ferroptotic trigger waves involves recurrent activation of cellular redox switches through diffusive ROS signals, cascading like dominoes from one cell to the next. The research team employed 24-hour time-lapse imaging and quantitative image analysis to find that ferroptotic trigger waves propagate over long distances at a constant speed. Chen likened this process to sculpting art, where large-scale cell death clears extensive temporary tissues.

The first authors are Ms. Hannah Katrina C. Co, an international Ph.D. student in the Taiwan International Graduate Program - Molecular and Cell Biology (TIGP-MCB), at Academia Sinica, and Dr. Chia-Chou Wu, a postdoctoral research fellow in the Lab for Cell Dynamics. Co described how ferroptotic cell death propagates through a cell population via self-regenerating ROS wave fronts. Wu likened constructing a mathematical model for the ferroptotic trigger waves to assembling building blocks: selecting and arranging equations to resemble the regulatory logic underlying dynamics of ferroptotic trigger waves. Next, the team aims to uncover transmitting ferroptosis-inducing molecules and structures of tissue-specific signaling networks for large-scale cell death in different embryo regions.

Investigates the Emergence of Cell Death Memory during Evolution; Presents New Avenues for Cancer Therapy in Biomedical Research

During embryonic development, both cell proliferation and death are essential for organogenesis. This pioneering research underscores the utilization of ferroptosis trigger waves as a tissue-sculpting mechanism during embryonic development. Since when and how organisms evolve mechanisms to control the initiation and propagation of cell death waves remains mysterious. The understandings of which will provide new insights for developing novel strategies for cancer therapy in biomedical research. 

1 Reactive Oxygen Species (ROS) are unstable molecules containing oxygen that readily react with other molecules within cells. Accumulation of ROS can lead to damage in DNA, RNA, and proteins, and can cause cell death.

2 ROS Feedback Loops include the iron-mediated Fenton reaction, NADPH oxidase signaling, and the glutathione synthesis pathway.

Media Contact Close
  • Dr. Sheng-Hong Chen, Institute of Molecular Biology, Academia Sinica

    (02)-2789-9318,shengchen@gate.sinica.edu.tw

  • Mr. Astin Chang, Media & Public Affairs, Secretariat, Academia Sinica

    (02) 2787-2565,astinchang@as.edu.tw

  • Ms. Steffi Tung Lin, Media & Public Affairs, Secretariat, Academia Sinica

    (02) 2789-8820,tunglin@as.edu.tw

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