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  3. Epiblast inducers capture mouse trophectoderm stem cells in vitro and pattern blastoids for implantation in utero

Epiblast inducers capture mouse trophectoderm stem cells in vitro and pattern blastoids for implantation in utero

  • Cell Stem Cell. 2022 Jul 7;29(7):1102-1118.e8. doi: 10.1016/j.stem.2022.06.002.
Jinwoo Seong 1,  Javier Frias-Aldeguer 2,  Viktoria Holzmann 1,  Harunobu Kagawa 1,  Giovanni Sestini 1,  Heidar Heidari Khoei 3,  Yvonne Scholte Op Reimer 1,  Maarten Kip 4,  Saurabh J Pradhan 1,  Lucas Verwegen 5,  Judith Vivié 4,  Linfeng Li 6,  Anna Alemany 4,  Jeroen Korving 4,  Frank Darmis 4,  Alexander van Oudenaarden 4,  Derk Ten Berge 5,  Niels Geijsen 7,  Nicolas C Rivron 8
Affiliations

Affiliations

  • 1 Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna Biocenter, Vienna, Austria.
  • 2 Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, the Netherlands; Maastricht University, Maastricht, the Netherlands.
  • 3 Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna Biocenter, Vienna, Austria; Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
  • 4 Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, the Netherlands.
  • 5 Department of Cell Biology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.
  • 6 Maastricht University, Maastricht, the Netherlands.
  • 7 Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, the Netherlands; Department of Anatomy and Embryology, LUMC, Leiden University, Leiden, the Netherlands.
  • 8 Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna Biocenter, Vienna, Austria; Hubrecht Institute for Developmental Biology and Stem Cell Research, Utrecht, the Netherlands; Maastricht University, Maastricht, the Netherlands. Electronic address: nicolas.rivron@imba.oeaw.ac.at.
PMID: 35803228 DOI: 10.1016/j.stem.2022.06.002
Abstract

The embryo instructs the allocation of cell states to spatially regulate functions. In the blastocyst, patterning of trophoblast (TR) cells ensures successful implantation and placental development. Here, we defined an optimal set of molecules secreted by the epiblast (inducers) that captures in vitro stable, highly self-renewing mouse trophectoderm stem cells (TESCs) resembling the blastocyst stage. When exposed to suboptimal inducers, these stem cells fluctuate to form interconvertible subpopulations with reduced self-renewal and facilitated differentiation, resembling peri-implantation cells, known as TR stem cells (TSCs). TESCs have enhanced capacity to form blastoids that implant more efficiently in utero due to inducers maintaining not only local TR proliferation and self-renewal, but also WNT6/7B secretion that stimulates uterine decidualization. Overall, the epiblast maintains sustained growth and decidualization potential of abutting TR cells, while, as known, distancing imposed by the blastocyst cavity differentiates TR cells for uterus adhesion, thus patterning the essential functions of implantation.

Keywords

blastocyst, blastoid, induction, trophoblast stem cells, trophectoderm stem cells, trophectoderm, implantation, decidualization.

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