Other Seminars Sheng-Hong Chen

16/07/202610:00CHARLES DARWINOther SeminarsSheng-Hong ChenAcademia Sinica"The Spatial Logic of Cell Death: Ferroptotic Trigger Waves, Self-Organization, and Tissue Morphogenesis"Host: Lin, Hsiu-ChuanAbstract:Large-scale cell death is essential for tissue sculpting during development, yet how death events are coordinated across millimeter-scale tissues remains poorly understood. I will discuss our recent work revealing that ferroptosis, an iron- and lipid-peroxidation-dependent form of cell death, can propagate through cell populations as self-regenerating trigger waves of reactive oxygen species. These waves arise when ferroptotic stress converts cellular redox networks into bistable media, enabling local death events to spread over long distances through coupled ROS amplification and diffusion. In the developing avian limb, ferroptosis accompanies spatially restricted tissue remodeling, suggesting that ferroptotic waves can act as a developmental sculpting mechanism.
I will then present new work showing that cellular self-organization provides an additional layer of spatial control over ferroptosis propagation. In self-organized epithelial monolayers, active-nematic-like patterns of cell density and alignment encode distinct ferroptosis-sensitive and ferroptosis-resistant states: low-density, misaligned regions exhibit elevated YAP/TEAD1 activity and preferentially initiate ferroptosis, whereas high-density, aligned regions show increased NRF2 expression and form propagation-resistant boundaries. At the single-cell scale, elongation polarizes oxidizable lipids toward cell poles, biasing lipid peroxidation and ferroptosis propagation along the axis of cell alignment. Together, these mechanisms convert otherwise isotropic, unbounded ferroptotic trigger waves into anisotropic and spatially confined waves.
These findings suggest a systems-level view of regulated cell death in which biochemical feedback, lipid organization, and multicellular patterning jointly determine where cell death begins, how it spreads, and where it stops. More broadly, they raise the possibility that developmental tissues use self-organized physical patterns, alongside genetic and morphogenetic cues, to control collective cell fate during morphogenesis and stress adaptation.