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

Published version
Peer-reviewed

Type

Article

Change log

Authors

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

Abstract

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.

Description

Keywords

Animals, Blastocyst, Cadherins, Embryonic Stem Cells, Endoderm, Germ Layers, Mammals

Journal Title

Nat Cell Biol

Conference Name

Journal ISSN

1465-7392
1476-4679

Volume Title

24

Publisher

Springer Science and Business Media LLC
Sponsorship
European Research Council (669198)
Wellcome Trust (207415/Z/17/Z)