Transition states and cell fate decisions in epigenetic landscapes

Waddington's epigenetic landscape is an abstract metaphor frequently used to represent the relationship between gene activity and cell fates during development. Over the past few years, it has become a useful framework for interpreting results from single-cell transcriptomics experiments. It has led to the proposal that, during fate transitions, cells experience smooth, continuous progressions of global transcriptional activity, which can be captured by (pseudo)temporal dynamics. Here, focusing strictly on the fate decision events, we suggest an alternative view: that fate transitions occur in a discontinuous, stochastic manner whereby signals modulate the probability of the transition events.