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Updated: Sep 26, 2026

Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
Published on: June 6, 2017
Theoretical and experimental evidence for hysteresis in cell proliferation
Shaochun Bai1, David Goodrich, C Dennis Thron
1Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
Abstract:
We propose a mathematical model for the regulation of the G1-phase of the mammalian cell cycle taking into account interactions of cyclin D/cdk4, cyclin E/cdk2, Rb and E2F. Mathematical analysis of this model predicts that a change in the proliferative status in response to a change in concentrations of serum growth factors will exhibit the property of hysteresis: the concentration of growth factors required to induce proliferation is higher than the concentration required to maintain proliferation. We experimentally confirmed this prediction in mouse embryonic fibroblasts in vitro. In agreement with the mathematical model, this indicates that changes in proliferative mode caused by small changes in concentrations of growth factors are not easily reversible. Based on this study, we discuss the importance of proliferation hysteresis for cell cycle regulation.
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