An article from PNAS earlier this year examines how adult stem cells regulate differentiation, proliferation and apoptosis through crosstalk between genetic and epigenetic regulation. These three processes are important in organs and tissues to maintain cell populations that undergo stochastic fluctuations and genetic mutations over the course of a lifetime. The authors take a mathematical approach, without considering molecular details, to show how control strategies of these three processes during cell division may be chosen to maximize expected performance. Their model incorporates the performance functions of stem cells at two time scales: the time of one cell cycle and the lifetime of the tissue. Their model includes a feedback regulation that controls proliferation through both the cell population and heterogenous dependence on the epigenetic states, which is different than the typical feedback model that only depends on the size of the cell population. The model accounts for the elimination of genetically mutated cells by depending on apoptosis at each cell cycle. The authors suggest that this apoptosis maximizes the efficiency of stem cell regulation and demonstrates the cross-talk between DNA variants and epigenetics.