The landscape of regulated cell death: It's all downhill from here

Cells can die via any of several forms of regulated cell death (RCD), including apoptosis, pyroptosis, and necroptosis. We now appreciate that there is substantial crosstalk between them, allowing for a high degree of plasticity downstream of cell death triggers. Understanding this is essential to delineate roles of RCD in development, homeostasis, tumor biology, and immunity; however, this crosstalk can make the fate of individual cells difficult to visualize. Here, we present a conceptual framework that builds on Waddington's landscape model of lineage commitment. On the landscape of RCD, live cells begin atop a "mountain," from which they roll down via "valleys" representing different cell death programs, potentially being diverted or even raised back to the summit by regulators of these processes. While acknowledging that, like any conceptual framework, this visualization is imperfect, we hope it presents a succinct approach to understand the complexities and interconnections of cell death regulation.