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Chemically-defined induction of a primitive endoderm and epiblast-like niche supports post-implantation progression from blastoids

Erik J. Vrij, Yvonne S. Scholte op Reimer, Javier Frias Aldeguer, Isabel Misteli Guerreiro, Jop Kind, Bon-Kyoung Koo, Clemens A. van Blitterswijk, Nicolas C. Rivron
doi: https://doi.org/10.1101/510396
Erik J. Vrij
1MERLN Institute for Technology-inspired Regenerative Medicine, Maastricht University, The Netherlands
2IMBA - Institute of Molecular Biotechnology GmbH, Vienna, Austria
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  • For correspondence: nicolasrivron@gmail.com erikvrij@gmail.com
Yvonne S. Scholte op Reimer
1MERLN Institute for Technology-inspired Regenerative Medicine, Maastricht University, The Netherlands
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Javier Frias Aldeguer
1MERLN Institute for Technology-inspired Regenerative Medicine, Maastricht University, The Netherlands
3Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands
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Isabel Misteli Guerreiro
3Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands
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Jop Kind
3Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands
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Bon-Kyoung Koo
2IMBA - Institute of Molecular Biotechnology GmbH, Vienna, Austria
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Clemens A. van Blitterswijk
1MERLN Institute for Technology-inspired Regenerative Medicine, Maastricht University, The Netherlands
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Nicolas C. Rivron
1MERLN Institute for Technology-inspired Regenerative Medicine, Maastricht University, The Netherlands
3Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands
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  • For correspondence: nicolasrivron@gmail.com erikvrij@gmail.com
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Abstract

The early mammalian conceptus (blastocyst) contains two supporting extraembryonic tissues - the trophectoderm and the primitive endoderm (PrE) - that encase and guide the epiblast (Epi) to eventually form the all body. Modifications of the conceptus exposed key genes regulating these tissues co-development. However, the combinations of signalling pathways underlying the interplay of PrE and Epi remains elusive. Stem cell-based models including embryoid bodies and blastoids can be generated in large numbers and subjected to high-content screens. Here, we use combinatorial screens of proteins, GPCR ligands and small molecules to rapidly (72 hours) and efficiently (80%) guide embryoid bodies to form a three-dimensional PrE-/Epiblast-like niche in chemically-defined conditions (gel-free, serum-free). This bipotent niche spontaneously progresses, without growth factors, to form a pro-amniotic cavity surrounded by a polarized Epi covered with parietal and visceral endoderm-like cells. In blastoids, these molecules enhance the ratio and number of Gata6+/Nanog+ cells and promote the survival, expansion and morphogenesis of a post-implantation-like Epi in vitro. Altogether, modelling early development in chemically-defined conditions delineates the pathways sufficient to form a functional PrE/Epiblast niche that fuels post-implantation development.

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Posted April 12, 2019.
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Chemically-defined induction of a primitive endoderm and epiblast-like niche supports post-implantation progression from blastoids
Erik J. Vrij, Yvonne S. Scholte op Reimer, Javier Frias Aldeguer, Isabel Misteli Guerreiro, Jop Kind, Bon-Kyoung Koo, Clemens A. van Blitterswijk, Nicolas C. Rivron
bioRxiv 510396; doi: https://doi.org/10.1101/510396
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Chemically-defined induction of a primitive endoderm and epiblast-like niche supports post-implantation progression from blastoids
Erik J. Vrij, Yvonne S. Scholte op Reimer, Javier Frias Aldeguer, Isabel Misteli Guerreiro, Jop Kind, Bon-Kyoung Koo, Clemens A. van Blitterswijk, Nicolas C. Rivron
bioRxiv 510396; doi: https://doi.org/10.1101/510396

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