Human blastoids model blastocyst development and implantation

Harunobu Kagawa, Alok Javali, Heidar Heidari Khoei, Theresa Maria Sommer, Giovanni Sestini, Maria Novatchkova, Yvonne Scholte op Reimer, Gaël Castel, Alexandre Bruneau, Nina Maenhoudt, Jenna Lammers, Sophie Loubersac, Thomas Freour, Hugo Vankelecom, Laurent David and Nicolas Rivron ()
Additional contact information
Harunobu Kagawa: Vienna BioCenter (VBC)
Alok Javali: Vienna BioCenter (VBC)
Heidar Heidari Khoei: Vienna BioCenter (VBC)
Theresa Maria Sommer: Vienna BioCenter (VBC)
Giovanni Sestini: Vienna BioCenter (VBC)
Maria Novatchkova: Vienna BioCenter (VBC)
Yvonne Scholte op Reimer: Vienna BioCenter (VBC)
Gaël Castel: Université de Nantes, CHU Nantes, INSERM, Centre de Recherche en Transplantation et Immunologie
Alexandre Bruneau: Université de Nantes, CHU Nantes, INSERM, Centre de Recherche en Transplantation et Immunologie
Nina Maenhoudt: KU Leuven, (University of Leuven)
Jenna Lammers: Université de Nantes, CHU Nantes, INSERM, Centre de Recherche en Transplantation et Immunologie
Sophie Loubersac: Université de Nantes, CHU Nantes, INSERM, Centre de Recherche en Transplantation et Immunologie
Thomas Freour: Université de Nantes, CHU Nantes, INSERM, Centre de Recherche en Transplantation et Immunologie
Hugo Vankelecom: KU Leuven, (University of Leuven)
Laurent David: Université de Nantes, CHU Nantes, INSERM, Centre de Recherche en Transplantation et Immunologie
Nicolas Rivron: Vienna BioCenter (VBC)

Nature, 2022, vol. 601, issue 7894, 600-605

Abstract: Abstract One week after fertilization, human embryos implant into the uterus. This event requires the embryo to form a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Stem cells can form a blastocyst model that we called a blastoid1. Here we show that naive human pluripotent stem cells cultured in PXGL medium2 and triply inhibited for the Hippo, TGF-β and ERK pathways efficiently (with more than 70% efficiency) form blastoids generating blastocyst-stage analogues of the three founding lineages (more than 97% trophectoderm, epiblast and primitive endoderm) according to the sequence and timing of blastocyst development. Blastoids spontaneously form the first axis, and we observe that the epiblast induces the local maturation of the polar trophectoderm, thereby endowing blastoids with the capacity to directionally attach to hormonally stimulated endometrial cells, as during implantation. Thus, we propose that such a human blastoid is a faithful, scalable and ethical model for investigating human implantation and development3,4.

Date: 2022
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DOI: 10.1038/s41586-021-04267-8

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