Epiblast inducers capture mouse trophectoderm stem cells in vitro and pattern blastoids for implantation in utero
Year: 2022
Type: article
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.
Source: Cell stem cell
Authors: Jinwoo Seong, Javier Frias-Aldeguer, Viktoria Holzmann, Harunobu Kagawa, Giovanni Sestini, Heidar Heidari Khoei, Yvonne Scholte Op Reimer, Maarten Kip, Saurabh J. Pradhan, Lucas Verwegen, Judith Vivié, Linfeng Li, Anna Alemany, Jeroen Korving, Frank Darmis, Alexander van Oudenaarden, Derk ten Berge, Niels Geijsen, Nicolas C. Rivron
Institutions: Institute of Molecular Biotechnology, Austrian Academy of Sciences, Vienna Biocenter, Maastricht University, Hubrecht Institute for Developmental Biology and Stem Cell Research, Royan Institute, Academic Center for Education, Culture and Research, Erasmus MC, Leiden University, Leiden University Medical Center
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $8,900
Funders: Human Frontier Science Program, Boehringer Ingelheim, European Commission, Human Frontier Science Program, Boehringer Ingelheim Fonds, Austrian Science Fund, Horizon 2020 Framework Programme, European Research Council, Japan Society for the Promotion of Science, Horizon 2020, H2020 Marie Skłodowska-Curie Actions, HORIZON EUROPE Marie Sklodowska-Curie Actions, HORIZON EUROPE European Research Council
OpenAlex ID: W4284886829