Stem cell fate decisions: Substates and attractors

Heterogeneity of gene expression is a characteristic of stem cell populations. Here, we review our own findings with human pluripotent stem cells, emphasizing their capacity to occupy distinct metastable substates that influence their differentiation outcomes. Experimental studies, such as single-cell transcriptomics and analyses of marker dynamics, demonstrate the transient and dynamic nature of these substates. Based on a novel approach to model sequences of fluorescent marker distributions over time, we suggest that transitions between these substates may be governed by deterministic chaos in addition to stochastic fluctuations of gene expression, both of which likely contribute to the observed dynamic behavior.