Self-Organization of Mouse Stem Cells into an Extended Potential Blastoid

• Published in: Developmental cell Vol. 51; no. 6; pp. 698 - 712.e8
• Main Authors: Sozen, Berna, Cox, Andy L., De Jonghe, Joachim, Bao, Min, Hollfelder, Florian, Glover, David M., Zernicka-Goetz, Magdalena
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.12.2019
• Subjects: Animals; Blastocyst - cytology; Blastoid; Cell Differentiation - physiology; Cell Lineage - physiology; Development; Embryo; Embryo Implantation - physiology; Embryo, Mammalian - metabolism; Embryonic Development - physiology; Endoderm; Endoderm - cytology; Extended pluripotency; Gene Expression Regulation, Developmental; In Vitro; Mice; Mouse Embryonic Stem Cells - cytology; Preimplantation; Stem cells; Trophoblast; Embryo; Preimplantation; Stem cells; Development; In Vitro; Trophoblast; Blastoid; Extended pluripotency; Endoderm
• ISSN: 1534-5807; 1878-1551; 1878-1551
• DOI: 10.1016/j.devcel.2019.11.014

Mammalian blastocysts comprise three distinct cell lineages essential for development beyond implantation: the pluripotent epiblast, which generates the future embryo, and surrounding it the extra-embryonic primitive endoderm and the trophectoderm tissues. Embryonic stem cells can reintegrate into embryogenesis but contribute primarily to epiblast lineages. Here, we show that mouse embryonic stem cells cultured under extended pluripotent conditions (EPSCs) can be partnered with trophoblast stem cells to self-organize into blastocyst-like structures with all three embryonic and extra-embryonic lineages. Morphogenetic and transcriptome profiling analyses reveal that these blastocyst-like structures show distinct embryonic-abembryonic axes and primitive endoderm differentiation and can initiate the transition from the pre- to post-implantation egg cylinder morphology in vitro. [Display omitted] •Cell fate under extended potential conditions bifurcate to form EPI and PE-like lineages•EPSCs and TSCs self-organize into EPS-blastoids, resembling the late-stage blastocysts•EPS-blastoids undertake pre- to post-implantation transition in vitro•EPS-blastoids initiate implantation in vivo Sozen et al. demonstrate the generation of mammalian blastocyst-like structures from mouse EPSCs and TSCs that contain three spatially segregated lineages representative of the epiblast, trophectoderm, and primitive endoderm. These lineages can generate their descendants as development progresses and form egg cylinder morphology in vitro by effective endoderm programming.