Emergence and universality in the regulation of stem cell fate

03 Oct 2017

The mechanisms that control cell fate behaviour during development, and the factors leading to their dysregulation in disease, remain the subject of interest and debate. Lately, advances in single-cell genomics have shifted emphasis towards the elucidation of molecular regulatory programmes and transcriptional cell states. However, quantitative statistical approaches based on cell lineage tracing data have provided fresh insight into stem and progenitor cell behaviour, questioning the role of cell fate stochasticity, transcriptional heterogeneity and state priming. These investigations, which draw upon conceptual insights from statistical physics and mathematics, provide a novel, generic and rigorous framework to resolve and classify stem cell self-renewal strategies, which heavily constrain, but do not seek to define, underlying molecular mechanistic programmes. Here, using epithelial maintenance as an exemplar, we consider the foundation, conceptual basis, utility and limitations of such quantitative approaches in cell biology.