Induction of peri-implantation stage synthetic embryos using reprogramming paradigms in ESCs

Langkabel, J.; Horne, A.; Bonaguro, L.; Hesse, T.; Knaus, A.; Riedel, Y.; Händler, K.; Bassler, K.; Reusch, N.; Yeghiazarian, L. H.; Pecht, T.; Aschenbrenner, A. C.; Kaiser, F.; Kubaczka, C.; Schultze, J. L.; Schorle, H.

doi:10.1101/2021.01.25.428068

bioRxiv · 10.1101/2021.01.25.428068

Induction of peri-implantation stage synthetic embryos using reprogramming paradigms in ESCs

Langkabel, J.·Horne, A.·Bonaguro, L.·Hesse, T.·Knaus, A.·Riedel, Y.·Händler, K.·Bassler, K.·Reusch, N.·Yeghiazarian, L. H.·Pecht, T.·Aschenbrenner, A. C.·Kaiser, F.·Kubaczka, C.·Schultze, J. L.·Schorle, H.

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Abstract

Blastocyst-derived stem cell lines were shown to self-organize into embryo-like structures in 3D cell culture environments. Here, we provide evidence that synthetic embryo-like structures are generated solely based on transcription factor-mediated molecular reprogramming of embryonic stem cells in a simple 3D co-culture system. ESCs in these cultures self-organize into elongated, compartmentalized synthetic embryo-like structures over the course of reprogramming exhibiting anterior visceral endoderm formation and symmetry breaking. Single-cell RNA-Seq reveals transcriptional profiles resembling epiblast, visceral endoderm, and extraembryonic ectoderm of early murine embryos around E4.5-E5.5. Within the epiblast, compartment marker gene expression supports primordial germ cell specification. After transplantation, synthetic embryo-like structures implant in uteri and initiate the formation of decidual tissues. This system allows for fast and reproducible generation of synthetic embryo-like structures, providing further insights into synthetic embryology.

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Langkabel, J., Horne, A., Bonaguro, L., Hesse, T., Knaus, A., Riedel, Y., Händler, K., Bassler, K., Reusch, N., Yeghiazarian, L. H., Pecht, T., Aschenbrenner, A. C., Kaiser, F., Kubaczka, C., Schultze, J. L., Schorle, H.. 2021-01-25. Induction of peri-implantation stage synthetic embryos using reprogramming paradigms in ESCs. https://doi.org/10.1101/2021.01.25.428068

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