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

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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 embryonic 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 suppression gradually increases DNA methylation genome wide and repressive mark deposition at Nanog. Interestingly, 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.

Original languageEnglish
Article number112380
JournalCell Reports
Issue number4
Number of pages27
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s)

    Research areas

  • cell identity, chromatin, CP: Developmental biology, CP: Stem cell research, embryoids, embryonic stem cells, epigenetics, gastruloids, microfluidics, SUMOylation, synthetic embryos

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