Journal
NATURE MATERIALS
Volume 16, Issue 4, Pages 419-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NMAT4829
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Funding
- National Science Foundation [CMMI 1129611, CBET 1149401]
- National Institutes of Health [R21 EB017078, R01 EB019436, R01 DK089933]
- American Heart Association [12SDG12180025]
- University of Michigan Rackham Predoctoral Fellowship
- Directorate For Engineering [1149401] Funding Source: National Science Foundation
- Div Of Chem, Bioeng, Env, & Transp Sys [1149401] Funding Source: National Science Foundation
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Amniogenesis-the development of amnion-is a critical developmental milestone for early human embryogenesis and successful pregnancy(1,2). 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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