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Jun 22, 2022
Revealing primate-unique extraembryonic differentiation route by stem cell modeling

Masatoshi Ohgushi1、Nobuko Tanniyama 1、Alex Vandenbon 1、Mototsugu Eiraku1,2
(1 Institute for Life and Medical Sciences Kyoto University、2 Institute for Advanced Study of Human Biology)

Delamination of trophoblast-like syncytia from the amniotic ectodermal analogue in human primed embryonic stem cell-based differentiation model

Cell Reports (2022) doi.org/10.1016/j.celrep.2022.110973

Genetic studies using the mouse as model animal have revealed the framework of mammalian development. However, recent progress in primate embryology has unveiled substantial differences between mouse and human development, and the importance of analyses using human materials has been recognized. Nevertheless, ethical and technical hurdles hampered us to study early human development, especially in the peri-implantation stage. We addressed this issue by utilizing human embryonic stem cells (ESCs), which correspond to the post-implantation human epiblasts.

In this study, we focused on the extraembryonic tissues such as placenta and amnion, both of which are known to play important roles in fetus growth. First, we established an in vitro differentiation protocol that was supposed to recapitulate human amniogenesis. Using this protocol, we demonstrated that cells akin to syncytiotrophoblasts, a component of placental tissues, were delaminated from the amniotic ectodermal analogues. Since STBs had been shown to be raised from the trophectoderm layer of mouse blastocysts, the derivation of STB-like cells from human primed ESCs was a surprising observation that might challenge the conventional views of mammalian development. This finding suggests the primate-unique mode of extraembryonic tissue formation.

Human ESCs and iPSCs hold great potential as replenishable resources for the development of cell therapies and for use in drug discovery. In addition, they provide an excellent in vitro system to understand early human developmental processes, including cell differentiation or fate determination. The results reported in this study provide valuable information about the molecular basis underlying pregnancy-associated disorders such as fetus miscarriage and growth retention.