CaltechAUTHORS
  A Caltech Library Service

Self-organization of the in vitro attached human embryo

Deglincerti, Alessia and Croft, Gist F. and Pietila, Lauren N. and Zernicka-Goetz, Magdalena and Siggia, Eric D. and Brivanlou, Ali H. (2016) Self-organization of the in vitro attached human embryo. Nature, 533 (7602). pp. 251-254. ISSN 0028-0836. doi:10.1038/nature17948. https://resolver.caltech.edu/CaltechAUTHORS:20190405-170314964

[img] Image (JPEG) (Extended Data Figure 1 : Quantification of cells positive for transcriptional markers over d.p.f. 6–12 of in vitro culture) - Supplemental Material
See Usage Policy.

55kB
[img] Image (JPEG) (Extended Data Figure 2 : Human-specific transcriptional profiles of ICM and TE in d.p.f. 6 human blastocysts) - Supplemental Material
See Usage Policy.

96kB
[img] Image (JPEG) (Extended Data Figure 3 : Molecular signature of d.p.f. 8–10 embryos) - Supplemental Material
See Usage Policy.

122kB
[img] Image (JPEG) (Extended Data Figure 4 : Human-specific transcriptional profile of d.p.f. 10 embryos) - Supplemental Material
See Usage Policy.

108kB
[img] Image (JPEG) (Extended Data Figure 5 : Full z-series d.p.f. 10 amniotic and yolk sac cavities) - Supplemental Material
See Usage Policy.

216kB
[img] Image (JPEG) (Extended Data Figure 6 : Tilted three-dimensional reconstruction of a d.p.f. 12 embryo) - Supplemental Material
See Usage Policy.

145kB
[img] Image (JPEG) (Extended Data Figure 7 : Additional images from a d.p.f. 12 embryo) - Supplemental Material
See Usage Policy.

126kB
[img] PDF (Supplementary Table 1, which shows Cell scoring by marker and cell type) - Supplemental Material
See Usage Policy.

111kB
[img] Video (QuickTime) (Timecourse of in vitro human embryo attachment from DPF6 to DPF14) - Supplemental Material
See Usage Policy.

29MB
[img] Video (QuickTime) (Example of DPF6 embryo) - Supplemental Material
See Usage Policy.

29MB
[img] Video (QuickTime) (Example of DPF6 embryo) - Supplemental Material
See Usage Policy.

24MB
[img] Video (QuickTime) (Example of DPF8 embryo.) - Supplemental Material
See Usage Policy.

18MB
[img] Video (QuickTime) (Example of DPF10 embryo and cavitation) - Supplemental Material
See Usage Policy.

26MB
[img] Video (QuickTime) (Example of amniotic and yolk sac cavities in a DPF10 embryo) - Supplemental Material
See Usage Policy.

27MB
[img] Video (AVI) (Example of amniotic cavity in a DPF10 embryo) - Supplemental Material
See Usage Policy.

24MB
[img] Video (QuickTime) (Example of cytotrophoblast and syncytiotrophoblast phenotypes in a DPF12 embryo) - Supplemental Material
See Usage Policy.

24MB

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20190405-170314964

Abstract

Implantation of the blastocyst is a developmental milestone in mammalian embryonic development. At this time, a coordinated program of lineage diversification, cell-fate specification, and morphogenetic movements establishes the generation of extra-embryonic tissues and the embryo proper, and determines the conditions for successful pregnancy and gastrulation. Despite its basic and clinical importance, this process remains mysterious in humans. Here we report the use of a novel in vitro system1,2 to study the post-implantation development of the human embryo. We unveil the self-organizing abilities and autonomy of in vitro attached human embryos. We find human-specific molecular signatures of early cell lineage, timing, and architecture. Embryos display key landmarks of normal development, including epiblast expansion, lineage segregation, bi-laminar disc formation, amniotic and yolk sac cavitation, and trophoblast diversification. Our findings highlight the species-specificity of these developmental events and provide a new understanding of early human embryonic development beyond the blastocyst stage. In addition, our study establishes a new model system relevant to early human pregnancy loss. Finally, our work will also assist in the rational design of differentiation protocols of human embryonic stem cells to specific cell types for disease modelling and cell replacement therapy.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/nature17948DOIArticle
https://rdcu.be/bvFEzPublisherFree ReadCube access
ORCID:
AuthorORCID
Zernicka-Goetz, Magdalena0000-0002-7004-2471
Additional Information:© 2016 Nature Publishing Group. received 6 November 2015; accepted 30 March 2016. Published online 4 May 2016. We thank the members of the Brivanlou laboratory for their advice and criticisms, in particular C. Nchako, S. Tse for technical assistance, and members of the Zernicka-Goetz laboratory for their advice on how to culture embryos through attachment. We also thank A.K. Hadjantonakis for discussions, A. Wilkerson for support, and A. Brivanlou and P. Carleton-Evans for their comments on the manuscript. This work was supported by a STARR Foundation grant (number 2013-026) and Rockefeller Private funds. Images were obtained using instrumentation in The Rockefeller University Bio-Imaging Resource Center purchased with grant funds from the Sohn Conference Foundation. The Carnegie stage images are used with permission from the Virtual Human Embryo Project (http://virtualhumanembryo.lsuhsc.edu). We give special thanks for technical advice on imaging to A. North, K. Thomas, and P. Ariel, and on image analysis and rendering to T. Tong. This work would not have been possible without the generosity of the people who consented to donate their embryos to research, to whom we are indebted. Alessia Deglincerti & Gist F. Croft - These authors contributed equally to this work. Author Contributions: A.D., G.C., and L.P. performed experiments; A.D. and G.C. analysed experiments; M.Z.-G. was instrumental in teaching and transferring knowledge on the mouse technology to A.D.; E.S. provided criticism of the work and manuscript; A.H.B. conceived and designed the project, established contact with the source of the biological material, provided guidance and advice throughout the work, and interfaced with the Institutional Review Board at The Rockefeller University; all authors contributed to the manuscript. The authors declare no competing financial interests.
Funders:
Funding AgencyGrant Number
STARR Foundation2013-026
Rockefeller UniversityUNSPECIFIED
Sohn Conference FoundationUNSPECIFIED
Issue or Number:7602
DOI:10.1038/nature17948
Record Number:CaltechAUTHORS:20190405-170314964
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20190405-170314964
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:94536
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:09 Apr 2019 21:03
Last Modified:16 Nov 2021 17:05

Repository Staff Only: item control page