Semrau, StefanGoldmann, Johanna E.Soumillon, MagaliMikkelsen, Tarjei S.Jaenisch, Rudolfvan Oudenaarden, Alexander2017-12-062017Semrau, Stefan, Johanna E. Goldmann, Magali Soumillon, Tarjei S. Mikkelsen, Rudolf Jaenisch, and Alexander van Oudenaarden. 2017. “Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells.” Nature Communications 8 (1): 1096. doi:10.1038/s41467-017-01076-4. http://dx.doi.org/10.1038/s41467-017-01076-4.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34492502Gene expression heterogeneity in the pluripotent state of mouse embryonic stem cells (mESCs) has been increasingly well-characterized. In contrast, exit from pluripotency and lineage commitment have not been studied systematically at the single-cell level. Here we measure the gene expression dynamics of retinoic acid driven mESC differentiation from pluripotency to lineage commitment, using an unbiased single-cell transcriptomics approach. We find that the exit from pluripotency marks the start of a lineage transition as well as a transient phase of increased susceptibility to lineage specifying signals. Our study reveals several transcriptional signatures of this phase, including a sharp increase of gene expression variability and sequential expression of two classes of transcriptional regulators. In summary, we provide a comprehensive analysis of the exit from pluripotency and lineage commitment at the single cell level, a potential stepping stone to improved lineage manipulation through timing of differentiation cues.en-USJournal Article2017-12-0610.1038/s41467-017-01076-4