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

The control of biophysical cues during the culture of human pluripotent stem cells on biomaterial substrates can be used to replicate the in vivo amniogenic environment and direct in vitro generation of early human amniotic tissue. 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.