Adult stem cells are functionally defined by the dual capabilities of self-renewal (which maintains the stem cell pool) and differentiation (which generates the different cell types of a particular lineage). Lineage hierarchies of stem, progenitor and differentiated cells underlie the homeostatic turnover of numerous tissues, and deviations in homeostasis can have severe pathological consequences. However, the general principles that underpin stem cell dynamics in these contexts are still incompletely understood. A new paper in Development from Philip Greulich and colleagues analyses the architecture of such lineages from a network theory approach. After formally defining cell types by their potential (the set of cell states they can arrive at), the authors then construct cell state networks, in which the cell states are the nodes and cell state trajectories the links between them. From this network, another can be derived in which cell types are represented as nodes. Analysis of this network shows that cell types are necessarily arranged in a hierarchy. When such networks are restricted by the imposition of homeostasis (where the number of cells of each type should stay constant over time), self-renewing cell types necessarily reside at the apex of cell lineage hierarchies; hence, self-renewal and lineage potential are intrinsically coupled properties. Finally, the authors define how feedback from the environment (for instance, from a stem cell niche) can determine ‘stemness’ in any cell type at the apex of the lineage hierarchy. This work emphasises the utility of network theory to understand the fundamentals of stem cell dynamics.
