Stem cell-derived synthetic embryos self-assemble by exploiting cadherin codes and cortical tension.

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Bao, Min 
Cornwall-Scoones, Jake 
Sanchez-Vasquez, Estefania 
Chen, Dong-Yuan 
De Jonghe, Joachim 

Mammalian embryos sequentially differentiate into trophectoderm and an inner cell mass, the latter of which differentiates into primitive endoderm and epiblast. Trophoblast stem (TS), extraembryonic endoderm (XEN) and embryonic stem (ES) cells derived from these three lineages can self-assemble into synthetic embryos, but the mechanisms remain unknown. Here, we show that a stem cell-specific cadherin code drives synthetic embryogenesis. The XEN cell cadherin code enables XEN cell sorting into a layer below ES cells, recapitulating the sorting of epiblast and primitive endoderm before implantation. The TS cell cadherin code enables TS cell sorting above ES cells, resembling extraembryonic ectoderm clustering above epiblast following implantation. Whereas differential cadherin expression drives initial cell sorting, cortical tension consolidates tissue organization. By optimizing cadherin code expression in different stem cell lines, we tripled the frequency of correctly formed synthetic embryos. Thus, by exploiting cadherin codes from different stages of development, lineage-specific stem cells bypass the preimplantation structure to directly assemble a postimplantation embryo.

Animals, Blastocyst, Cadherins, Embryonic Stem Cells, Endoderm, Germ Layers, Mammals
Journal Title
Nat Cell Biol
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Springer Science and Business Media LLC
European Research Council (669198)
Wellcome Trust (207415/Z/17/Z)