Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells
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s41467-017-01076-4.pdf
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Author(s)
Semrau, Stefan
Goldmann, Johanna E.
Soumillon, Magali
Mikkelsen, Tarjei S.
Jaenisch, Rudolf
van Oudenaarden, Alexander
Date Issued
October 2017
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Semrau, Stefan et al. “Dynamics of Lineage Commitment Revealed by Single-Cell Transcriptomics of Differentiating Embryonic Stem Cells.” Nature Communications 8, 1 (October 2017): 1096 © 2017 The Author(s)
Version
Final published version
Abstract
Gene 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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1038/S41467-017-01076-4
