PNAS Plus Significance Statements

Abstract

This paper examines how adult stem cells maintain their ability to carry out a complex set of tasks, including tissue regeneration and replacement of defective cells. To do so, stem cell populations must coordinate differentiation, proliferation, and cell death (apoptosis) to maintain an appropriate distribution of epigenetic states. Using the tools of applied mathematics, and borrowing from the theory of intergenerational transfer of resources, this paper (pp. E880-E887) shows how control strategies during cell division should be chosen to maximize expected performance, utilizing cross-talk between genetic and epigenetic regulation and performance criteria during homeostasis. Heterogeneous proliferation, a mixed strategy in which not all cells have the same proliferation probability, is shown to increase robustness, and hence long-term performance.