Dynamics of a single cell fate decision

As an animal develops from a fertilized egg into a complex multicellular organism, its cells change from being pluripotent to lineage restricted. These state changes are often driven by morphogens, molecules that launch signalling cascades that affect DNA transcription and modify a cell’s protein makeup. While morphogens and cell fates have been extensively identified, the process through which a morphogen changes a cell’s fate is not well understood. To elucidate these dynamics, we performed bulk RNA sequencing at multiple time points during a single cell fate decision in which pluripotent Xenopus laevis (African frog) cells differentiate to one of two fates: neural progenitor and epidermis. We found that the geometric structure of both transitions include linear temporal trends that correspond with development toward a neural fate, and that epidermal fated cells exhibit a second, non-linear temporal trend that corresponds with BMP activation. Our analyses enabled us to predict a point-of-no-return for the epidermal fate, which we experimentally verified. Our work highlights the importance of examining intermediate developmental times to discern fate specification, and sheds light on distinguishing the internal and external forces that drive embryonic development.