Dynamics of Lineage Commitment Revealed by Single-Cell Transcriptomics of Differentiating Embryonic Stem Cells

Nat Commun. 2017 Oct 23;8(1):1096. doi: 10.1038/s41467-017-01076-4.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Embryonic Stem Cells / cytology*
  • Embryonic Stem Cells / metabolism
  • Gene Expression Regulation, Developmental
  • Mice
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / metabolism
  • Proteins / genetics
  • Proteins / metabolism
  • Single-Cell Analysis*
  • Transcriptome*

Substances

  • Proteins