Self-organization of post-implantation-like embryonic tissues from blastoids

Vrij, E. J.; Scholte Op Reimer, Y.; Frias Aldeguer, J.; Misteli Guerreiro, I.; Kind, J.; Koo, B.-K.; van Blitterswijk, C.; Rivron, N.

doi:10.1101/510396

bioRxiv · 10.1101/510396

Self-organization of post-implantation-like embryonic tissues from blastoids

Vrij, E. J.·Scholte Op Reimer, Y.·Frias Aldeguer, J.·Misteli Guerreiro, I.·Kind, J.·Koo, B.-K.·van Blitterswijk, C.·Rivron, N.

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Abstract

The early mammalian embryo (blastocyst) contains three co-developing types of stem cells. Two supporting extraembryonic types - the trophectoderm and the primitive endoderm - encase and guide the pluripotent epiblast that eventually forms all body tissues. Unlike embryos, stem cell-based models of the embryo can be generated in large numbers and subjected to high-content screens as a basis for basic and biomedical discoveries (Rivron et al., 2018a; Vrij et al., 2016b). Here, we show that aggregates of naive Embryonic stem cells cultured in chemically-defined conditions and exposed to combinatorial screens of signaling molecules, rapidly (48 hours) and efficiently (80%) set apart PrE-like cells. These cells produce a basal lamina, generate progenitors resembling both visceral and parietal endoderm, and polarize co-developing Epiblast cells to form a proamniotic cavity. In blastoids, stem cell-based models of the early blastocyst (Rivron et al., 2018b), this combination of signals increases the ratio and number of Gata6+/Nanog+ cells and promotes the survival, growth and morphogenesis of a post-implantation-like Epiblast in vitro. Modeling early embryonic development in chemically-defined in vitro conditions shows that the primitive endoderm forms via a specific combination of signaling pathways and sufficient to drive the development of the Epiblast.

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Vrij, E. J., Scholte Op Reimer, Y., Frias Aldeguer, J., Misteli Guerreiro, I., Kind, J., Koo, B.-K., van Blitterswijk, C., Rivron, N.. 2019-01-02. Self-organization of post-implantation-like embryonic tissues from blastoids. https://doi.org/10.1101/510396

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