Disproportionate feedback interactions govern cell-type specific proliferation in mammalian cells

Abstract

AbstractIn mammalian cells, the critical decision to maintain quiescence over proliferation commitment in and around the G1-S transition depends on more than one intertwined feedback interaction, and is highly cell-type dependent. However, the precise role played by these individual feedback regulations, in order to generate such diverse nature of proliferation commitment, is still poorly understood. Herein, we propose a generic mathematical model of G1-S transition in mammalian cells that not only reconciles distinct single cell experimental observations in a cell-type specific manner, but also makes experimentally testable non-intuitive predictions. Intriguingly, The model analysis reveals that the feedback motifs responsible for the G1-S transition act in a disparate fashion to organize the cell-type specific proliferation response in different mammalian cells. The proposed model, in principle, can be effectively tuned to explore proliferation dynamics in a cell-type specific way to gain crucial insights about novel therapeutic intervention to prevent unwanted cellular proliferation.