A pluripotent stem cell-based model for post-implantation human amniotic sac development

TLDR

Amniotic sac formation is a critical early event in human implantation, yet its developmental mechanisms remain poorly understood. The authors aim to create a human pluripotent stem cell–based model, the post‑implantation amniotic sac embryoid (PASE), to recapitulate early amniotic sac development. PASE is generated from hPSCs and self‑organizes into an epithelial cyst with an asymmetric amniotic ectoderm‑epiblast pattern, mimicking the human amniotic sac. PASE recapitulates key developmental events: it forms an asymmetric cyst, initiates a SNAI1‑dependent posterior primitive streak–like process, displays asymmetric BMP‑SMAD signaling, and BMP‑SMAD modulation controls stable development, revealing a novel hPSC fate potential and a platform for human embryology.

Abstract

Development of the asymmetric amniotic sac-with the embryonic disc and amniotic ectoderm occupying opposite poles-is a vital milestone during human embryo implantation. Although essential to embryogenesis and pregnancy, amniotic sac development in humans remains poorly understood. Here, we report a human pluripotent stem cell (hPSC)-based model, termed the post-implantation amniotic sac embryoid (PASE), that recapitulates multiple post-implantation embryogenic events centered around amniotic sac development. Without maternal or extraembryonic tissues, the PASE self-organizes into an epithelial cyst with an asymmetric amniotic ectoderm-epiblast pattern that resembles the human amniotic sac. Upon further development, the PASE initiates a process that resembles posterior primitive streak development in a SNAI1-dependent manner. Furthermore, we observe asymmetric BMP-SMAD signaling concurrent with PASE development, and establish that BMP-SMAD activation/inhibition modulates stable PASE development. This study reveals a previously unrecognized fate potential of human pluripotent stem cells and provides a platform for advancing human embryology.Early in human embryonic development, it is unclear how amniotic sac formation is regulated. Here, the authors use a human pluripotent stem cell-based model, termed the post-implantation amniotic sac embryoid, to recapitulate early embryogenic events of human amniotic sac development.