Physiological significance of polyploidization in mammalian cells

•Polyploidization occurs in selected mammalian cell types during development, aging, cancer, tissue regeneration, and degeneration.•Polyploidization is a stress response and creates genetic diversity for better stress adaptation.•Genetic mouse models with diminished polyploidization are powerful tools to determine the biological function of polyploidization.

Programmed polyploidization occurs in all mammalian species during development and aging in selected tissues, but the biological properties of polyploid cells remain obscure. Spontaneous polyploidization arises during stress and has been observed in a variety of pathological conditions, such as cancer and degenerative diseases. A major challenge in the field is to test the predicted functions of polyploidization in vivo. However, recent genetic mouse models with diminished polyploidization phenotypes represent novel, powerful tools to unravel the biological function of polyploidization. Contrary to a longstanding hypothesis, polyploidization appears to not be required for differentiation and has no obvious impact on proliferation. Instead, polyploidization leads to increased cell size and genetic diversity, which could promote better adaptation to chronic injury or stress. We discuss here the consequences of reducing polyploidization in mice and review which stress responses and molecular signals trigger polyploidization during development and disease.