Transient suppression of SUMOylation in embryonic stem cells generates embryo-like structures
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Transient suppression of SUMOylation in embryonic stem cells generates embryo-like structures. / Cossec, Jack Christophe; Traboulsi, Tatiana; Sart, Sébastien; Loe-Mie, Yann; Guthmann, Manuel; Hendriks, Ivo A.; Theurillat, Ilan; Nielsen, Michael L.; Torres-Padilla, Maria Elena; Baroud, Charles N.; Dejean, Anne.
In: Cell Reports, Vol. 42, No. 4, 112380, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Transient suppression of SUMOylation in embryonic stem cells generates embryo-like structures
AU - Cossec, Jack Christophe
AU - Traboulsi, Tatiana
AU - Sart, Sébastien
AU - Loe-Mie, Yann
AU - Guthmann, Manuel
AU - Hendriks, Ivo A.
AU - Theurillat, Ilan
AU - Nielsen, Michael L.
AU - Torres-Padilla, Maria Elena
AU - Baroud, Charles N.
AU - Dejean, Anne
N1 - Publisher Copyright: © 2023 The Author(s)
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - cell identity
KW - chromatin
KW - CP: Developmental biology
KW - CP: Stem cell research
KW - embryoids
KW - embryonic stem cells
KW - epigenetics
KW - gastruloids
KW - microfluidics
KW - SUMOylation
KW - synthetic embryos
U2 - 10.1016/j.celrep.2023.112380
DO - 10.1016/j.celrep.2023.112380
M3 - Journal article
C2 - 37061916
AN - SCOPUS:85152458544
VL - 42
JO - Cell Reports
JF - Cell Reports
SN - 2211-1247
IS - 4
M1 - 112380
ER -
ID: 345374069