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

Bao, Min and Cornwall-Scoones, Jake and Sánchez-Vásquez, Estefania and Chen, Dong-Yuan and De Jonghe, Joachim and Shadkhoo, Shahriar and Hollfelder, Florian and Thomson, Matt and Glover, David M. and Zernicka-Goetz, Magdalena (2022) Stem cell-derived synthetic embryos self-assemble by exploiting cadherin codes and cortical tension. Nature Cell Biology, 24 (9). pp. 1341-1349. ISSN 1465-7392. PMCID PMC9481465. doi:10.1038/s41556-022-00984-y.

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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.

Item Type:Article
Related URLs:
URLURL TypeDescription ReadCube access CentralArticle
Bao, Min0000-0003-0992-9388
Cornwall-Scoones, Jake0000-0002-7435-486X
Shadkhoo, Shahriar0000-0003-3582-0634
Hollfelder, Florian0000-0002-1367-6312
Thomson, Matt0000-0003-1021-1234
Glover, David M.0000-0003-0956-0103
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:This work was supported by the Wellcome Trust (207415/Z/17/Z), an European Research Council advanced grant (669198), a National Institutes of Health R01 (HD100456-01A1) grant, the National Institutes of Health Pioneer Award (DP1 HD104575-01), the Tianqiao and Chrissy Chen Institute for Neuroscience and Shurl and Kay Curci Foundation grants to M.Z.-G. E.S.-V. is supported by a Pew Latin America fellowship. M.B. is supported by a Caltech Postdoctoral Fellowship. We thank the Life Science Foundation, members of the M.Z.-G. laboratory and A. Winkel for invaluable comments and suggestions.
Group:Tianqiao and Chrissy Chen Institute for Neuroscience
Funding AgencyGrant Number
Wellcome Trust207415/Z/17/Z
European Research Council (ERC)669198
NIHDP1 HD104575-01
Tianqiao and Chrissy Chen Institute for NeuroscienceUNSPECIFIED
Shurl and Kay Curci FoundationUNSPECIFIED
Pew Latin American Fellows ProgramUNSPECIFIED
Caltech Postdoctoral FellowshipUNSPECIFIED
Issue or Number:9
PubMed Central ID:PMC9481465
Record Number:CaltechAUTHORS:20220919-149101800
Persistent URL:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:117071
Deposited By: Melissa Ray
Deposited On:21 Sep 2022 16:19
Last Modified:21 Sep 2022 16:19

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