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Inducible Stem-Cell-Derived Embryos Capture Mouse Morphogenetic Events In Vitro

Amadei, Gianluca and Lau, Kasey Y. C. and De Jonghe, Joachim and Gantner, Carlos W. and Sozen, Berna and Chan, Christopher and Zhu, Meng and Kyprianou, Christos and Hollfelder, Florian and Zernicka-Goetz, Magdalena (2021) Inducible Stem-Cell-Derived Embryos Capture Mouse Morphogenetic Events In Vitro. Developmental Cell, 56 (3). pp. 366-382. ISSN 1534-5807. PMCID PMC7883308. https://resolver.caltech.edu/CaltechAUTHORS:20210104-164232285

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Abstract

The development of mouse embryos can be partially recapitulated by combining embryonic stem cells (ESCs), trophoblast stem cells (TS), and extra-embryonic endoderm (XEN) stem cells to generate embryo-like structures called ETX embryos. Although ETX embryos transcriptionally capture the mouse gastrula, their ability to recapitulate complex morphogenic events such as gastrulation is limited, possibly due to the limited potential of XEN cells. To address this, we generated ESCs transiently expressing transcription factor Gata4, which drives the extra-embryonic endoderm fate, and combined them with ESCs and TS cells to generate induced ETX embryos (iETX embryos). We show that iETX embryos establish a robust anterior signaling center that migrates unilaterally to break embryo symmetry. Furthermore, iETX embryos gastrulate generating embryonic and extra-embryonic mesoderm and definitive endoderm. Our findings reveal that replacement of XEN cells with ESCs transiently expressing Gata4 endows iETX embryos with greater developmental potential, thus enabling the study of the establishment of anterior-posterior patterning and gastrulation in an in vitro system.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1016/j.devcel.2020.12.004DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883308PubMed CentralArticle
ORCID:
AuthorORCID
Sozen, Berna0000-0001-5834-5819
Zhu, Meng0000-0001-6157-8840
Kyprianou, Christos0000-0001-8516-9195
Hollfelder, Florian0000-0002-1367-6312
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2020 The Authors. Under a Creative Commons license - Attribution 4.0 International (CC BY 4.0) Received 26 May 2020, Revised 26 October 2020, Accepted 4 December 2020, Available online 29 December 2020. We thank Marta Shahbazi, Neophytos Christodoulou, and David Glover for their advice and the members of the MZG laboratory for their feedback and encouragement. This work was supported by a European Research Council Grant (RG77946), Wellcome Trust (207415/Z/17/Z), Open Philanthropy, Shurl and Kay Curci, and Weston Havens Foundations grants awarded to M.Z.G.; K.Y.C.L. is supported by the Croucher Foundation and Cambridge Trust. F.H. is supported by a European Research Council Grant (695669) and Wellcome Trust (WT108438/C/15/Z). J.D.J. is supported by the Biotechnology and Biological Sciences Research Council. Author contributions. G.A. conceived the study and performed the work with the help of K.Y.C.L., C.W.G., C.C., and B.S. J.D.J. performed the single-cell sequencing analysis. F.H. supervised the single-cell sequencing analysis. M.Z. performed the chimera experiments. C.K. contributed to the live imaging. The study was supervised by M.Z.G. G.A. and M.Z.G. wrote the paper, with the help of K.Y.C.L., C.W.G., and J.D.J. The authors declare no competing interests.
Funders:
Funding AgencyGrant Number
European Research Council (ERC)RG77946
Wellcome Trust207415/Z/17/Z
Open PhilanthropyUNSPECIFIED
Shurl and Kay Curci FoundationUNSPECIFIED
Weston Havens FoundationUNSPECIFIED
Croucher FoundationUNSPECIFIED
Cambridge TrustUNSPECIFIED
European Research Council (ERC)695669
Wellcome TrustWT108438/C/15/Z
Biotechnology and Biological Sciences Research Council (BBSRC)UNSPECIFIED
Subject Keywords:induced ETX-embryos; stem cells; gastrulation; EMT; embryogenesis; gastruloid
Issue or Number:3
PubMed Central ID:PMC7883308
Record Number:CaltechAUTHORS:20210104-164232285
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20210104-164232285
Official Citation:Gianluca Amadei, Kasey Y.C. Lau, Joachim De Jonghe, Carlos W. Gantner, Berna Sozen, Christopher Chan, Meng Zhu, Christos Kyprianou, Florian Hollfelder, Magdalena Zernicka-Goetz, Inducible Stem-Cell-Derived Embryos Capture Mouse Morphogenetic Events In Vitro, Developmental Cell, Volume 56, Issue 3, 2021, Pages 366-382.e9, ISSN 1534-5807, https://doi.org/10.1016/j.devcel.2020.12.004.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:107313
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:05 Jan 2021 15:43
Last Modified:01 Mar 2021 17:35

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