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Nat Mater. 2017 Apr;16(4):419-425. doi: 10.1038/nmat4829. Epub 2016 Dec 12.

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

Author information

1
Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
2
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
3
Institute of Environmental Health Sciences, Wayne State University, Detroit, MI 48202, USA.
4
Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, 48109, USA.
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Contributed equally

Abstract

Amniogenesis-the development of amnion-is a critical developmental milestone for early human embryogenesis and successful pregnancy. 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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