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Embryonic signals perpetuate polar-like trophoblast stem cells and pattern the blastocyst axis

Javier Frias-Aldeguer, Maarten Kip, Judith Vivié, Linfeng Li, Anna Alemany, Jeroen Korving, Frank Darmis, Alexander van Oudenaarden, Niels Geijsen, Nicolas C. Rivron
doi: https://doi.org/10.1101/510362
Javier Frias-Aldeguer
1MERLN Institute for Technology-inspired Regenerative Medicine, Maastricht University, The Netherlands
2Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands
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Maarten Kip
2Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands
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Judith Vivié
2Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands
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Linfeng Li
1MERLN Institute for Technology-inspired Regenerative Medicine, Maastricht University, The Netherlands
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Anna Alemany
2Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands
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Jeroen Korving
2Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands
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Frank Darmis
2Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands
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Alexander van Oudenaarden
2Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands
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Niels Geijsen
2Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands
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Nicolas C. Rivron
1MERLN Institute for Technology-inspired Regenerative Medicine, Maastricht University, The Netherlands
2Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, The Netherlands
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  • For correspondence: nicolasrivron@gmail.com
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Summary

The early mammalian conceptus (blastocyst) comprises an outer trophoblast globe that forms an axis originating from the inner embryonic cells. From the mouse conceptus, Trophoblast stem cells (TSCs) are derived, which are in vitro analogues of early trophoblasts. Here, we show that TSCs contain plastic subpopulations reflecting developmental states ranging from pre- to post-implantation trophoblasts. However, upon exposure to a specific combination of embryonic inductive signals, TSCs globally acquire properties of pre-implantation polar trophoblasts (gene expression, self-renewal) juxtaposing the inner embryonic cells, and an enhanced, homogeneous epithelial phenotype. These lines of polar-like TSCs (pTSCs) represent a transcriptionally earlier state that more efficiently forms blastoids, whose inner embryonic cells then induce the patterning of gene expression along the embryonic-abembryonic axis. Altogether, delineating the requirements and properties of polar trophoblasts and blastocyst axis formation in vitro provides a foundation for the precise description and dissection of early development.

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Posted January 13, 2020.
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Embryonic signals perpetuate polar-like trophoblast stem cells and pattern the blastocyst axis
Javier Frias-Aldeguer, Maarten Kip, Judith Vivié, Linfeng Li, Anna Alemany, Jeroen Korving, Frank Darmis, Alexander van Oudenaarden, Niels Geijsen, Nicolas C. Rivron
bioRxiv 510362; doi: https://doi.org/10.1101/510362
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Embryonic signals perpetuate polar-like trophoblast stem cells and pattern the blastocyst axis
Javier Frias-Aldeguer, Maarten Kip, Judith Vivié, Linfeng Li, Anna Alemany, Jeroen Korving, Frank Darmis, Alexander van Oudenaarden, Niels Geijsen, Nicolas C. Rivron
bioRxiv 510362; doi: https://doi.org/10.1101/510362

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