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Mechanics-guided embryonic patterning of neuroectoderm tissue from human pluripotent stem cells

Nature Materialsvolume 17pages633641 (2018) | Download Citation

Abstract

Classic embryological studies have successfully applied genetics and cell biology principles to understand embryonic development. However, it remains unresolved how mechanics, as an integral driver of development, is involved in controlling tissue-scale cell fate patterning. Here we report a micropatterned human pluripotent stem (hPS)-cell-based neuroectoderm developmental model, in which pre-patterned geometrical confinement induces emergent patterning of neuroepithelial and neural plate border cells, mimicking neuroectoderm regionalization during early neurulation in vivo. In this hPS-cell-based neuroectoderm patterning model, two tissue-scale morphogenetic signals—cell shape and cytoskeletal contractile force—instruct neuroepithelial/neural plate border patterning via BMP-SMAD signalling. We further show that ectopic mechanical activation and exogenous BMP signalling modulation are sufficient to perturb neuroepithelial/neural plate border patterning. This study provides a useful microengineered, hPS-cell-based model with which to understand the biomechanical principles that guide neuroectoderm patterning and hence to study neural development and disease.

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Acknowledgements

We thank A. Liu for comments on the manuscript. This work is supported in part by the National Science Foundation (CMMI 1129611 and CBET 1149401 to J.F. and CMMI 1662835 to Y. Sun), the American Heart Association (12SDG12180025 to J.F.) and the Department of Mechanical Engineering at the University of Michigan. The Lurie Nanofabrication Facility at the University of Michigan, a member of the National Nanotechnology Infrastructure Network funded by the National Science Foundation, is acknowledged for support in microfabrication.

Author information

Author notes

  1. These authors contributed equally: Xufeng Xue and Yubing Sun

Affiliations

  1. Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA

    • Xufeng Xue
    • , Yubing Sun
    • , Agnes M. Resto-Irizarry
    • , Koh Meng Aw Yong
    • , Yi Zheng
    • , Shinuo Weng
    • , Yue Shao
    •  & Jianping Fu
  2. Department of Mechanical and Industrial Engineering, University of Massachusetts, Amherst, MA, USA

    • Yubing Sun
  3. School of the Gifted Young, University of Science and Technology of China, Hefei, China

    • Ye Yuan
  4. Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China

    • Yimin Chai
  5. Developmental Biology Program, Memorial Sloan-Kettering Institute, New York, NY, USA

    • Lorenz Studer
  6. Center of Stem Cell Biology, Memorial Sloan-Kettering Institute, New York, NY, USA

    • Lorenz Studer
  7. Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA

    • Jianping Fu
  8. Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA

    • Jianping Fu

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Contributions

Y. Sun, X.X. and J.F. designed experiments; X.X. and Y. Sun performed differentiation assays; A.R.-I. and Y. Sun developed MATLAB scripts for image processing; X.X., Y. Sun, K.M.A.Y., Y.Z., S.W. and Y. Shao generated and analysed gene expression data; X.X. and Y.Y. conducted cell migration assays; L.S. provided Sox10-EGFP cells; Y. Sun, X.X., Y.C. and J.F. analysed data and wrote the manuscript. J.F. supervised the entire project. All authors edited and approved the manuscript.

Competing interests

The authors declare no competing interests.

Corresponding authors

Correspondence to Yubing Sun or Jianping Fu.

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DOI

https://doi.org/10.1038/s41563-018-0082-9