A research team at Academia Sinica’s Institute of Molecular Biology has published findings on large-scale cell death during embryonic development, which it said can contribute to studies on cancer therapy by finding ways to inhibit tumor growth.
The process of rapid cell differentiation during early embryonic development in various lifeforms leading to growth of the multicelluar organism has been observed since the 19th century, but scientists were puzzled by the accompanying phase of massive cell death, Chen Sheng-hong (陳昇宏) and his team members said at a news conference in Taipei yesterday.
The team’s findings were published online this month in the science journal Nature, entitled, “Emergence of large-scale cell death through ferroptotic trigger wave,” which Chen coauthored with Hannah Katrina C. Co (許碧領), Wu Chia-chou (吳嘉洲) and Lee Yi-chen.
Photo: Chen Chia-yi, Taipei Times
The team discovered that reactive oxygen species (ROS) is the trigger that initiates the ferroptosis process, an iron and lipid-peroxidation-dependent form of programmed cell death, Chen said, adding that the process is biochemically distinct from other forms of regulated cell death.
The study can contribute to cancer therapy, as activation of the process plays a regulatory role on growth of tumor cells in the human body, he said.
The study found the mechanism for ROS in regulating the ferroptotic trigger wave, with the team showing color images of trigger waves of ferroptosis propagating outward from dead cells through lipid peroxidation signals at the wave fronts.
The results also indicated that ferroptotic stress through suppression of amino acid cysteine uptake activates the ROS feedback loops.
The team demonstrated that ferroptosis and its propagation accompany the massive, yet spatially restricted, cell death events in their research on muscle growth of embryonic avian limbs.
“Our findings highlight the role of ferroptosis in coordinating cell death events, providing a paradigm for investigating large-scale cell death in embryonic development and human pathologies,” Chen said.
Other team members showed research modeling and illustrations on 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.
Chen said the team used 24-hour time-lapse imaging to capture cellular activity, and found that the propagation wave was like creating a work of art, where large-scale cell death helped the growing embryo to clean up and sculpt new regions for cellular growth.
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