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Nat Commun . 2021 Dec 16

Induction of Rosette-to-Lumen stage embryoids using reprogramming paradigms in ESCs

Jan Langkabel, Arik Horne, Lorenzo Bonaguro, Lisa Holsten, Tatiana Hesse, Alexej Knaus, Yannick Riedel, Matthias Becker, Kristian Händler, Tarek Elmzzahi, Kevin Bassler, Nico Reusch, Leon Harootoonovtch Yeghiazarian, Tal Pecht, Adem Saglam, Thomas Ulas, Anna C Aschenbrenner, Franziska Kaiser, Caroline Kubaczka, Joachim L Schultze, Hubert Schorle

Blastocyst-derived stem cell lines were shown to self-organize into embryo-like structures in 3D cell culture environments. Here, we provide evidence that embryo-like structures can be generated solely based on transcription factor-mediated reprogramming of embryonic stem cells in a simple 3D co-culture system. Embryonic stem cells in these cultures self-organize into elongated, compartmentalized embryo-like structures reflecting aspects of the inner regions of the early post-implantation embryo. Single-cell RNA-sequencing reveals transcriptional profiles resembling epiblast, primitive-/visceral endoderm, and extraembryonic ectoderm of early murine embryos around E4.5-E5.5. In this stem cell-based embryo model, progression from rosette formation to lumenogenesis accompanied by progression from naïve- to primed pluripotency was observed within Epi-like cells. Additionally, lineage specification of primordial germ cells and distal/anterior visceral endoderm-like cells was observed in epiblast- or visceral endoderm-like compartments, respectively. The system presented in this study allows for fast and reproducible generation of embryo-like structures, providing an additional tool to study aspects of early embryogenesis.

PMID: 34916498