Dynamic post-transcriptional regulation during embryonic stem cell differentiation

Abstract

SummaryDuring in vitro differentiation, pluripotent stem cells undergo extensive remodeling of their gene expression profile. While studied extensively at the transcriptome level, much less is known about protein dynamics. Here, we measured mRNA and protein levels of 7459 genes during differentiation of embryonic stem cells (ESCs). This comprehensive data set revealed pervasive discordance between mRNA and protein. The high temporal resolution of the data made it possible to determine protein turnover rates genome-wide by fitting a kinetic model. This model further enabled us to systematically identify dynamic post-transcriptional regulation. Moreover, we linked different modes of regulation to the function of specific gene sets. Finally, we showed that the kinetic model can be applied to singlecell transcriptomics data to predict protein levels in differentiated cell types. In conclusion, our comprehensive data set, easily accessible through a web application, is a valuable resource for the discovery of post-transcriptional regulation in ESC differentiation.