Link to Pubmed [PMID] – 37061916
Link to DOI – 10.1016/j.celrep.2023.112380
Cell Rep . 2023 Apr 15;42(4):112380. doi: 10.1016/j.celrep.2023.112380
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.
Keywords: CP: Developmental biology; CP: Stem cell research; SUMOylation; cell identity; chromatin; embryoids; embryonic stem cells; epigenetics; gastruloids; microfluidics; synthetic embryos.
Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.