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Transient suppression of SUMOylation in embryonic stem cells generates embryo-like structures.
Cell Rep. 42:112380 (2023)
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.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Cp: Developmental Biology ; Cp: Stem Cell Research ; Sumoylation ; Cell Identity ; Chromatin ; Embryoids ; Embryonic Stem Cells ; Epigenetics ; Gastruloids ; Microfluidics ; Synthetic Embryos
ISSN (print) / ISBN
2211-1247
e-ISSN
2211-1247
Zeitschrift
Cell Reports
Quellenangaben
Band: 42,
Heft: 4,
Artikelnummer: 112380
Verlag
Cell Press
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute of Epigenetics and Stem Cells (IES)