Synthetic Ex Utero Embryogenesis: from Naive Pluripotent Stem Cells to Advanced Whole Embryoids

The identity of somatic and pluripotent cells can be epigenetically reprogrammed and forced to adapt a new functional cell state by different methods and distinct combinations of exogenous factors. The aspiration to utilize such in vitor reprogrammed pluripotent and somatic cells for therapeutic purposes necessitates understanding of the mechanisms of reprogramming and differentiation and elucidating the extent of equivalence of the in vitro derived cells to their in vivo counterparts. In my presentation, I will present my group’s recent advances toward understanding these fundamental questions and further detail our ongoing efforts to generate developmentally unrestricted human naive pluripotent cells with embryonic and extra-embryonic developmental potential. I will expand on new avenues for utilizing custom made electronically controlled ex utero platforms and optimized conditions for growing natural mammalian embryos ex utero for extended periods capturing both the gastrulation and organogenesis until advanced stages, for better studying of stem cell transitions during embryogenesis and organogenesis. I will detail how the latter platforms offered an exclusive technical platform to demonstrate and unleash the self-organizing capacity of mouse naïve PSCs to generate post-gastrulation organ-filled whole synthetic embryos with both embryonic and extraembryonic compartment ex utero. Collectively, I will be highlighting prospects for new platforms for advancing human disease and developmental modelling.