Post-Gastrulation Synthetic Embryos Generated Ex Utero from Mouse Naïve ESCs

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)3290-3306.e25
JournalCell
Volume185
Issue number18
Early online date2 Aug 2022
DOIs
StatePublished - 1 Sep 2022

Keywords

  • Animals
  • Cell Differentiation/physiology
  • ESCs
  • Embryo, Mammalian/physiology
  • Embryonic Development
  • Embryonic Stem Cells
  • Endoderm
  • Gastrulation
  • Mammals
  • Mice
  • PGCs
  • embryogenesis
  • embryoids
  • ex utero
  • extra-embryonic Tissues
  • iPSCs
  • naive pluripotency
  • synthetic embryos

All Science Journal Classification (ASJC) codes

  • General Biochemistry,Genetics and Molecular Biology

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