The hand that carves life --- Ferroptosis Trigger Waves

During embryonic development, cells proliferate rapidly and differentiate to form the tissues and organs of multicellular organisms. Paradoxically, these processes that foster the creation of life is often accompanied by large-scale cell death, observed since the 18th century. Such death events can sometimes cover large areas of tissue, causing cell death of millions of cells. However, the mechanism by which large-scale cell death occurs and its functional role in development remain a century-old mystery. Sheng-hong Chen’s research team (Lab for Cell Dynamics: https://celldynamicslab.mystrikingly.com) has provided an explanation for this century-old mystery. They found that large-scale cell death can occur through reactive oxygen species (ROS)-mediated ferroptosis trigger waves. Different from simple diffusion whereby a signal dissipates quickly in space, trigger waves are self-regenerating chemical wave fronts that propagate at a constant speed over long distances. Using chemical and genetic perturbations, mathematical modeling, and computer simulations, Sheng-hong Chen’s team demonstrated the primary role of ROS feedback loops (iron-mediated Fenton reaction, NADPH oxidase signaling, and the glutathione synthesis pathway) in the occurrence and progression of ferroptosis trigger waves. During embryonic development, ferroptosis trigger waves occur to eliminate large areas of temporary tissues that no longer serve a purpose for the mature organism, substantiating its utility as a tissue-sculpting strategy for organogenesis. These research results were published in Nature, July this year (2024). The first authors of this paper are Hannah Katrina C. Co, a Ph.D. student of the TIGP MCB program, and Chia-Chou Wu, a postdoctoral research fellow. This study is supported by funding from the Institute of Molecular Biology and grants from Academia Sinica to S.-h.C. (AS-GCS-111-L04 and AS-GCP-113-L02).