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

TY - JOUR

T1 - Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells

AU - Semrau, Stefan

AU - Goldmann, Johanna E

AU - Soumillon, Magali

AU - Mikkelsen, Tarjei S

AU - Jaenisch, Rudolf

AU - van Oudenaarden, Alexander

PY - 2017/10/23

Y1 - 2017/10/23

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1038/s41467-017-01076-4

DO - 10.1038/s41467-017-01076-4

M3 - Article

C2 - 29061959

SN - 2041-1723

VL - 8

SP - 1096

JO - Nature Communications

JF - Nature Communications

IS - 1

ER -