Efficient generation of ETX embryoids that recapitulate the entire window of murine egg cylinder development

Cathérine Dupont; Olivier J.M. Schäffers; Beatrice F. Tan; Sarra Merzouk; Eric M. Bindels; An Zwijsen; Danny Huylebroeck; Joost Gribnau

doi:10.1126/sciadv.add2913

Efficient generation of ETX embryoids that recapitulate the entire window of murine egg cylinder development

Cathérine Dupont^*, Olivier J.M. Schäffers, Beatrice F. Tan, Sarra Merzouk, Eric M. Bindels, An Zwijsen, Danny Huylebroeck, Joost Gribnau

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

10 Citations (Scopus)

Abstract

The murine embryonic–trophoblast–extra-embryonic endoderm (ETX) model is an integrated stem cell–based model to study early postimplantation development. It is based on the self-assembly potential of embryonic, trophoblast, and hypoblast/primitive/visceral endoderm-type stem cell lines (ESC, TSC, and XEN, respectively) to arrange into postimplantation egg cylinder–like embryoids. Here, we provide an optimized method for reliable and efficient generation of ETX embryoids that develop into late gastrulation in static culture conditions. It is based on transgenic Gata6-overproducing ESCs and modified assembly and culture conditions. Using this method, up to 43% of assembled ETX embryoids exhibited a correct spatial distribution of the three stem cell derivatives at day 4 of culture. Of those, 40% progressed into ETX embryoids that both transcriptionally and morphologically faithfully mimicked in vivo postimplantation mouse development between E5.5 and E7.5. The ETX model system offers the opportunity to study the murine postimplantation egg cylinder stages and could serve as a source of various cell lineage precursors.

Original language	English
Article number	eadd2913
Journal	Science advances
Volume	9
Issue number	3
DOIs	https://doi.org/10.1126/sciadv.add2913 https://doi.org/10.1126/sciadv.add2913
Publication status	Published - 18 Jan 2023

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Copyright © 2023 The Authors, some rights reserved;

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title = "Efficient generation of ETX embryoids that recapitulate the entire window of murine egg cylinder development",

abstract = "The murine embryonic–trophoblast–extra-embryonic endoderm (ETX) model is an integrated stem cell–based model to study early postimplantation development. It is based on the self-assembly potential of embryonic, trophoblast, and hypoblast/primitive/visceral endoderm-type stem cell lines (ESC, TSC, and XEN, respectively) to arrange into postimplantation egg cylinder–like embryoids. Here, we provide an optimized method for reliable and efficient generation of ETX embryoids that develop into late gastrulation in static culture conditions. It is based on transgenic Gata6-overproducing ESCs and modified assembly and culture conditions. Using this method, up to 43% of assembled ETX embryoids exhibited a correct spatial distribution of the three stem cell derivatives at day 4 of culture. Of those, 40% progressed into ETX embryoids that both transcriptionally and morphologically faithfully mimicked in vivo postimplantation mouse development between E5.5 and E7.5. The ETX model system offers the opportunity to study the murine postimplantation egg cylinder stages and could serve as a source of various cell lineage precursors.",

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AU - Bindels, Eric M.

AU - Zwijsen, An

AU - Huylebroeck, Danny

AU - Gribnau, Joost

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Efficient generation of ETX embryoids that recapitulate the entire window of murine egg cylinder development

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