The University of Hong Kong, China (People's Republic)
Abstract: Novel stem cell technologies to generate preimplantation embryo-like structures in large numbers and for high-content screens would help alleviate the need for human embryos to gain fundamental knowledge on human early embryo development and implantation. Using human expanded potential stem cells (hEPSCs), we demonstrate that aggregates of hEPSCs in 3D culture recapitulate key signatures of the human morula, particularly in terms of polarity establishment and activated YAP signalling in the polarized outer cells. These hEPSC-derived morula-like structures (moruloids) develop into blastocyst-like structures (blastoids) composed of three pre-implantation lineages including the epiblast, the trophectoderm and the hypoblast via the triple inhibition of the MEK/ERK, TGFβ and Hippo pathways. Mechanistically, we revealed that TFAP2C regulates the aPKC-dependent polarity establishment in moruloids, which is necessary for blastoid generation. Moreover, the hEPSC-derived blastoids further develop into human pre-gastrulation embryoids with the respective amniotic and yolk sac cavities upon in vitro implantation, recapitulating human peri- and post-implantation developmental milestones. Overall, our newly established human early embryo models from hEPSCs provide an in vitro platform for elucidating the molecular mechanisms orchestrating early human embryogenesis.
Funding Source:
Funding: This project is supported by Health@InnoHK, Innovation Technology Commission, HKSAR
