Fig. 1: Instability during differentiation provides an opportunity for assessment of individual cellular phenotypes present in a heterogeneous differentiating population.

In the above figure, a progenitor cell prior to differentiation is at a multipotent state (1). Acquisition of epimutations or other forms of heritable cellular diversity, as represented by dotted or dashed outlines (2), can alter the propensities of descendent cells toward attractor states. At the onset of differentiation (3), attractor states emerge, represented by depressions forming in the landscape. The adjacent presence of an apoptotic attractor state alongside a differentiation attractor state creates an unstable equilibrium (box). Differentiating cells proceed, balancing along this ridge until individual cellular phenotypes exert sufficient attraction toward either state (4), causing trajectories to diverge. Heterogeneous cells are consequently sorted into differentiated or apoptotic fates, with apoptotic cells terminating progress in an inescapable well (5).