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

In mammalian cells, the decision to maintain quiescence over proliferation commitment during 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 organizing such diverse proliferation dynamics is still poorly understood. Herein, we propose a predictive mathematical model of G1 -S transition in mammalian cells that reconciles distinct single-cell experimental observations in a cell-type specific manner. 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. Importantly, the proposed model can be effectively tuned to gain insights into the proliferation commitment of diverse mammalian cell types and can find wide applicability.