Post-gastrulation synthetic embryos generated ex utero from mouse naive ESCs

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Cell. 2022 Jul;185:3290-3306.e25. doi: https://doi.org/10.1016/j.cell.2022.07.028

Post-gastrulation synthetic embryos generated ex utero from mouse naive ESCs Aguilera Castrejon Lab

Tarazi Shadi, Aguilera-Castrejon Alejandro, Joubran Carine, Ghanem Nadir, Ashouokhi Shahd, Roncato Francesco, Wildschutz Emilie, Haddad Montaser, Oldak Bernardo, Gomez-Cesar Elidet, Livnat Nir, Viukov Sergey, Lokshtanov Dmitry, Naveh-Tassa Segev, Rose Max, Hanna Suhair, Raanan Calanit, Brenner Ori, Kedmi Merav, Keren-Shaul Hadas, Lapidot Tsvee, Maza Itay, Novershtern Noa, Hanna Jacob

Note: Research in this publication was not performed at Janelia.

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Abstract

Summary In vitro cultured stem cells with distinct developmental capacities can contribute to embryonic or extraembryonic 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 extraembryonic 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 extraembryonic compartments, starting solely from naive ESCs. This was achieved by co-aggregating non-transduced ESCs, with naive ESCs transiently expressing Cdx2 or Gata4 to promote their priming toward trophectoderm and primitive endoderm lineages, respectively. sEmbryos adequately accomplish gastrulation, advance through key developmental milestones, and develop organ progenitors within complex extraembryonic compartments similar to E8.5 stage mouse embryos. Our findings highlight the plastic potential of naive pluripotent cells to self-organize and functionally reconstitute and model the entire mammalian embryo beyond gastrulation.

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Post-gastrulation synthetic embryos generated ex utero from mouse naive ESCs

Note: Research in this publication was not performed at Janelia.

Abstract

Janelia Authors