“Post-Gastrulation Synthetic Embryos Generated Ex Utero from Mouse Naïve Embryonic Stem Cells”, Shadi Tarazi, Alejandro Aguilera-Castrejon, Carine Joubran, Nadir Ghanem, Shahd Ashouokhi, Francesco Roncato, Emilie Wildschutz, Montaser Haddad, Bernardo Oldak, Elidet Gomez-Cesar, Nir Livnat, Sergey Viukov, Dmitry Lukshtanov, Segev Naveh-Tassa, Max Rose, Suhair Hanna, Calanit Raanan, Ori Brenner, Merav Kedmi, Hadas Keren-Shaul, Tsvee Lapidot, Itay Maza, Noa Novershtern, Jacob H. Hann2022-08-01 (gametogenesis; backlinks)⁠:

• Advanced synthetic embryos (sEmbryos) self-assembled from ESCs in an ex utero setup

• Naïve ESCs give rise to all embryonic and extra-embryonic compartments in sEmbryos

• Post-gastrulation stem cell derived sEmbryos develop organ-specific progenitors

• Extra-embryonic compartments adequately develop in post-gastrulation whole sEmbryos

[video; media, cf. Zernicka-Goetz et al 2022, Amadei et al 2022] In vitro cultured stem cells with distinct developmental capacities can contribute to embryonic or extra-embryonic tissues after microinjection into pre-implantation mammalian embryos. However, whether cultured stem cells can independently give rise to entire gastrulating embryo-like structures with embryonic and extra-embryonic compartments, remains unknown.

Here we adapt a recently established platform for prolonged ex utero growth of natural embryos, to generate mouse post-gastrulation synthetic whole embryo models (sEmbryos), with both embryonic and extra-embryonic compartments, starting solely from naïve ESCs.

This was achieved by co-aggregating non-transduced ESCs, with naïve ESCs transiently expressing Cdx2 and Gata4 to promote their priming towards trophectoderm and primitive endoderm lineages, respectively. sEmbryos adequately accomplish gastrulation, advance through key developmental milestones, and develop organ progenitors within complex extra-embryonic compartments similar to E8.5 stage mouse embryos.

Our findings highlight the plastic potential of naïve pluripotent cells to self-organize and functionally reconstitute and model the entire mammalian embryo beyond gastrulation.

See Also:

• An extra-uterine system to physiologically support the extreme premature lamb

• Oocyte-induced haploidization

• Perspectives of germ cell development in vitro in mammals

• Functional Oocytes Derived from Granulosa Cells

• Generation of ovarian follicles from mouse pluripotent stem cells

• Successful Serial Recloning in the Mouse over Multiple Generations

• Generation of genome-edited dogs by somatic cell nuclear transfer

• Chromosome transplantation as a novel approach for correcting complex genomic disorders

• Correction of a pathogenic gene mutation in human embryos

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