Transient suppression of SUMOylation in embryonic stem cells generates embryo-like structures

Recent advances in synthetic embryology have opened new avenues for understanding the complex events controlling mammalian peri-implantation development. Here, we show that mouse embryonic stem cells (ESCs) solely exposed to chemical inhibition of SUMOylation generate embryo-like structures comprising anterior neural and trunk-associated regions. HypoSUMOylation-instructed ESCs give rise to spheroids that self-organize into gastrulating structures containing cell types spatially and functionally related to em-bryonic and extraembryonic compartments. Alternatively, spheroids cultured in a droplet microfluidic device form elongated structures that undergo axial organization reminiscent of natural embryo morphogenesis. Single-cell transcriptomics reveals various cellular lineages, including properly positioned anterior neuronal cell types and paraxial mesoderm segmented into somite-like structures. Transient SUMOylation suppres-sion gradually increases DNA methylation genome wide and repressive mark deposition at Nanog. Interest-ingly, cell-to-cell variations in SUMOylation levels occur during early embryogenesis. Our approach provides a proof of principle for potentially powerful strategies to explore early embryogenesis by targeting chromatin roadblocks of cell fate change.

Automated summary

Recent advances in synthetic embryology have revealed that chemical inhibition of SUMOylation in mouse embryonic stem cells (ESCs) can lead to the generation of embryo-like structures. These structures can self-organize into gastrulating structures and undergo axial organization reminiscent of natural embryo morphogenesis. This approach provides a proof of principle for exploring early embryogenesis by targeting chromatin roadblocks of cell fate change.