Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells

BioRxiv : the Preprint Server for Biology
Stefan SemrauAlexander van Oudenaarden

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 measured the gene expression dynamics of retinoic acid driven mESC differentiation using an unbiased single-cell transcriptomics approach. We found that the exit from pluripotency marks the start of a lineage bifurcation as well as a transient phase of susceptibility to lineage specifying signals. Our study revealed several transcriptional signatures of this phase, including a sharp increase of gene expression variability. Importantly, we observed a handover between two classes of transcription factors. The early-expressed class has potential roles in lineage biasing, the late-expressed class in lineage commitment. In summary, we provide a comprehensive analysis of lineage commitment at the single cell level, a potential stepping stone to improved lineage control through timing of differentiation cues.

Related Concepts

Cell Differentiation Process
Disease Susceptibility
Gene Expression
Retinoids
Transcription, Genetic
Comet Assay
Analysis
Human Embryonic Stem Cells
Protein Expression
Unbiased Estimation

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