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Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche

Nature Materials volume 16, pages 419–425 (2017)Cite this article

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Abstract

Amniogenesis—the development of amnion—is a critical developmental milestone for early human embryogenesis and successful pregnancy1,2. However, human amniogenesis is poorly understood due to limited accessibility to peri-implantation embryos and a lack of in vitro models. Here we report an efficient biomaterial system to generate human amnion-like tissue in vitro through self-organized development of human pluripotent stem cells (hPSCs) in a bioengineered niche mimicking the in vivo implantation environment. We show that biophysical niche factors act as a switch to toggle hPSC self-renewal versus amniogenesis under self-renewal-permissive biochemical conditions. We identify a unique molecular signature of hPSC-derived amnion-like cells and show that endogenously activated BMP–SMAD signalling is required for the amnion-like tissue development by hPSCs. This study unveils the self-organizing and mechanosensitive nature of human amniogenesis and establishes the first hPSC-based model for investigating peri-implantation human amnion development, thereby helping advance human embryology and reproductive medicine.

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Figure 1: hPSCs form squamous cysts with amnion-like morphology in an implantation-like niche.
Figure 2: Development of squamous cysts from hPSCs on a synthetic, soft artificial matrix.
Figure 3: Squamous cyst development is transcriptionally distinct from canonical EMT or primitive streak.
Figure 4: Molecular characterization and identification of the squamous, hPSC-derived amnion-like tissue.
Figure 5: Endogenously activated BMP–SMAD signalling is required for the development of hPSC-amnion.

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Acknowledgements

We thank K. S. O’Shea, S. Kalantry, T. Miki and W. Shawlot for comments on the manuscript. We are grateful to M. Czerwinski for help with bioinformatics. We thank G. D. Smith at the University of Michigan MStem Cell Laboratories for providing the UM63-1 hESC line and the University of Michigan Pluripotent Stem Cell Core and the Steven Schwartzberg Memorial Fund for the derivation of the 1196a hiPSC line. This work is supported by the National Science Foundation (CMMI 1129611 and CBET 1149401, J.F.), the National Institutes of Health (R21 EB017078 and R01 EB019436, J.F.; R01 DK089933, D.L.G.), and the American Heart Association (12SDG12180025, J.F.). Y.S. is also partially supported by the University of Michigan Rackham Predoctoral Fellowship. The Lurie Nanofabrication Facility at the University of Michigan, a member of the National Nanotechnology Infrastructure Network (NNIN) funded by the National Science Foundation, is acknowledged for support in microfabrication.

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Author notes

  1. Yue Shao and Kenichiro Taniguchi: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Mechanical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA

    Yue Shao, Xufeng Xue, Koh Meng Aw Yong, Jianming Sang & Jianping Fu

  2. Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA

    Kenichiro Taniguchi, Ryan F. Townshend, Jason R. Spence, Deborah L. Gumucio & Jianping Fu

  3. Institute of Environmental Health Sciences, Wayne State University, Detroit, Michigan 48202, USA

    Katherine Gurdziel

  4. Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan 48109, USA

    Jianping Fu

Authors
  1. Yue Shao
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Contributions

Y.S., K.T., D.L.G. and J.F. designed experiments; Y.S., K.T., R.F.T., X.X., K.M.A.Y. and J.S. performed experiments; K.G. processed RNA-seq results and performed hierarchical clustering; Y.S., K.T., K.G., J.R.S., D.L.G. and J.F. analysed data and wrote the manuscript. D.L.G. and J.F. supervised the project. All authors contributed to the manuscript.

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Correspondence to Deborah L. Gumucio or Jianping Fu.

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Shao, Y., Taniguchi, K., Gurdziel, K. et al. Self-organized amniogenesis by human pluripotent stem cells in a biomimetic implantation-like niche. Nature Mater 16, 419–425 (2017). https://doi.org/10.1038/nmat4829

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