Abstract

In adult, tissues are maintained and repaired by stem cells, which divide and differentiate to generate more specialized progeny. The mechanisms that control the balance between proliferation and differentiation promise fundamental insights into the origin and design of multi-cellular organisms. Using epidermis as a model system, we show how the combination of genetic lineage tracing assays in transgenic mouse models with simple ideas from non-equilibrium statistical physics provide a quantitative platform to resolve the stochastic fate behaviour of stem cells and their progeny in both healthy and diseased states. Furthermore, we describe how these methods can be adapted to address exome deep-sequening data, providing a new and general method to resolve the pattern of normal stem cell fate, and detect and characterize the mutational signature of rare field transformations in human tissues, with implications for the early detection of preneoplasia.