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

Author

Listed:
  • Stefan Semrau

    (Hubrecht Institute–KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht
    Whitehead Institute for Biomedical Research
    Leiden Institute of Physics)

  • Johanna E. Goldmann

    (Whitehead Institute for Biomedical Research)

  • Magali Soumillon

    (Broad Institute
    Harvard University)

  • Tarjei S. Mikkelsen

    (Broad Institute
    Harvard University)

  • Rudolf Jaenisch

    (Whitehead Institute for Biomedical Research
    Massachusetts Institute of Technology)

  • Alexander van Oudenaarden

    (Hubrecht Institute–KNAW (Royal Netherlands Academy of Arts and Sciences) and University Medical Center Utrecht)

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.

Suggested Citation

  • Stefan Semrau & Johanna E. Goldmann & Magali Soumillon & Tarjei S. Mikkelsen & Rudolf Jaenisch & Alexander van Oudenaarden, 2017. "Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells," Nature Communications, Nature, vol. 8(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01076-4
    DOI: 10.1038/s41467-017-01076-4
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    Cited by:

    1. Sébastien Durand & Marion Bruelle & Fleur Bourdelais & Bigitha Bennychen & Juliana Blin-Gonthier & Caroline Isaac & Aurélia Huyghe & Sylvie Martel & Antoine Seyve & Christophe Vanbelle & Annie Adrait , 2023. "RSL24D1 sustains steady-state ribosome biogenesis and pluripotency translational programs in embryonic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    2. Xinyu Hu & Bob van Sluijs & Óscar García-Blay & Yury Stepanov & Koen Rietrae & Wilhelm T. S. Huck & Maike M. K. Hansen, 2024. "ARTseq-FISH reveals position-dependent differences in gene expression of micropatterned mESCs," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Geethika Arekatla & Stavroula Skylaki & David Corredor Suarez & Hartland Jackson & Denis Schapiro & Stefanie Engler & Markus Auler & German Camargo Ortega & Simon Hastreiter & Andreas Reimann & Dirk L, 2024. "Identification of an embryonic differentiation stage marked by Sox1 and FoxA2 co-expression using combined cell tracking and high dimensional protein imaging," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    4. Rowan D Brackston & Eszter Lakatos & Michael P H Stumpf, 2018. "Transition state characteristics during cell differentiation," PLOS Computational Biology, Public Library of Science, vol. 14(9), pages 1-24, September.
    5. Sina Schumacher & Max Fernkorn & Michelle Marten & Rui Chen & Yung Su Kim & Ivan Bedzhov & Christian Schröter, 2024. "Tissue-intrinsic beta-catenin signals antagonize Nodal-driven anterior visceral endoderm differentiation," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    6. Paraskevi Athanasouli & Martina Balli & Anchel Jaime-Soguero & Annekatrien Boel & Sofia Papanikolaou & Bernard K. Veer & Adrian Janiszewski & Tijs Vanhessche & Annick Francis & Youssef El Laithy & Ant, 2023. "The Wnt/TCF7L1 transcriptional repressor axis drives primitive endoderm formation by antagonizing naive and formative pluripotency," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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