Exploring early extraembryonic cells of epiblast origin: Questions on human amniotic ectoderm and extraembryonic mesoderm

Extraembryonic tissues are essential for proper fetal development and exhibit great diversity across species. Despite its importance, human extraembryonic development has been relatively overlooked. Previously, we established an in vitro model to study human amniogenesis and extraembryonic mesoderm formation. In this article, I develop discussions on four topics inspired by this study: (1) Features of amniotic cell populations described to date. A recently reported early amniotic cell type is examined based on its signature genes to consider how this population should be incorporated into models of primate amniogenesis. (2) Molecular mechanisms underlying the effect of cell density in regulating non-neural ectoderm specification. Fate specification by positional cues in mouse is revisited and possible mechanisms are suggested by drawing insights from human epiblast models. (3) Potential applications of the three-dimensional culture we established. Primate amniotic ectoderm is postulated as a gastrulation-inducing signaling center, and our technique could be used to effectively model its interactions with epiblast. (4) Extraembryonic mesoderm development in human embryos. The obscure origin of primate extraembryonic mesoderm and implications from recent in vitro differentiation models using human pluripotent stem cells are explained. The key concepts explored here will stimulate further studies into both amnion and extraembryonic mesoderm during human and non-human primate development.