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Generation of organized germ layers from a single mouse embryonic stem cell

Author

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  • Yeh-Chuin Poh

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology
    College of Engineering, University of Illinois at Urbana-Champaign)

  • Junwei Chen

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology)

  • Ying Hong

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology)

  • Haiying Yi

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology)

  • Shuang Zhang

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology)

  • Junjian Chen

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology)

  • Douglas C. Wu

    (College of Engineering, University of Illinois at Urbana-Champaign)

  • Lili Wang

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology)

  • Qiong Jia

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology)

  • Rishi Singh

    (College of Engineering, University of Illinois at Urbana-Champaign)

  • Wenting Yao

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology)

  • Youhua Tan

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology
    College of Engineering, University of Illinois at Urbana-Champaign)

  • Arash Tajik

    (College of Engineering, University of Illinois at Urbana-Champaign)

  • Tetsuya S. Tanaka

    (University of Notre Dame
    University of Notre Dame)

  • Ning Wang

    (Laboratory for Cell Biomechanics and Regenerative Medicine, School of Life Science and Technology, Huazhong University of Science and Technology
    College of Engineering, University of Illinois at Urbana-Champaign)

Abstract

Mammalian inner cell mass cells undergo lineage-specific differentiation into germ layers of endoderm, mesoderm and ectoderm during gastrulation. It has been a long-standing challenge in developmental biology to replicate these organized germ layer patterns in culture. Here we present a method of generating organized germ layers from a single mouse embryonic stem cell cultured in a soft fibrin matrix. Spatial organization of germ layers is regulated by cortical tension of the colony, matrix dimensionality and softness, and cell–cell adhesion. Remarkably, anchorage of the embryoid colony from the 3D matrix to collagen-1-coated 2D substrates of ~1 kPa results in self-organization of all three germ layers: ectoderm on the outside layer, mesoderm in the middle and endoderm at the centre of the colony, reminiscent of generalized gastrulating chordate embryos. These results suggest that mechanical forces via cell–matrix and cell–cell interactions are crucial in spatial organization of germ layers during mammalian gastrulation. This new in vitro method could be used to gain insights on the mechanisms responsible for the regulation of germ layer formation.

Suggested Citation

  • Yeh-Chuin Poh & Junwei Chen & Ying Hong & Haiying Yi & Shuang Zhang & Junjian Chen & Douglas C. Wu & Lili Wang & Qiong Jia & Rishi Singh & Wenting Yao & Youhua Tan & Arash Tajik & Tetsuya S. Tanaka & , 2014. "Generation of organized germ layers from a single mouse embryonic stem cell," Nature Communications, Nature, vol. 5(1), pages 1-12, September.
  • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms5000
    DOI: 10.1038/ncomms5000
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    Cited by:

    1. Bas Loo & Simone A. Den & Nuno Araújo-Gomes & Vincent Jong & Rebecca R. Snabel & Maik Schot & José M. Rivera-Arbeláez & Gert Jan C. Veenstra & Robert Passier & Tom Kamperman & Jeroen Leijten, 2023. "Mass production of lumenogenic human embryoid bodies and functional cardiospheres using in-air-generated microcapsules," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

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