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

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

doi:10.1016/j.stem.2022.06.002

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

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^*

^*Corresponding author for this work

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

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.

Original language	English
Pages (from-to)	1102-1118.e8
Number of pages	26
Journal	Cell stem cell
Volume	29
Issue number	7
DOIs	https://doi.org/10.1016/j.stem.2022.06.002
Publication status	Published - 7 Jul 2022

Keywords

ACTIVATED PROTEIN-KINASE
BLASTOCYST
CULTURE-CONDITIONS
EMBRYOS LACKING
ESSENTIAL REGULATOR
FATE DECISIONS
GENE-EXPRESSION
POTENTIAL ROLE
SELF-RENEWAL
TROPHOBLAST

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10.1016/j.stem.2022.06.002Licence: CC BY

Cite this

Seong, J., Frias-Aldeguer, J., Holzmann, V., Kagawa, H., Sestini, G., Heidari Khoei, H., Scholte Op Reimer, Y., Kip, M., Pradhan, S. J., Verwegen, L., Vivié, J., Li, L., Alemany, A., Korving, J., Darmis, F., van Oudenaarden, A., Ten Berge, D., Geijsen, N., & Rivron, N. C. (2022). Epiblast inducers capture mouse trophectoderm stem cells in vitro and pattern blastoids for implantation in utero. Cell stem cell, 29(7), 1102-1118.e8. https://doi.org/10.1016/j.stem.2022.06.002

@article{29f80e5494b949dfa387fd61455baaed,

title = "Epiblast inducers capture mouse trophectoderm stem cells in vitro and pattern blastoids for implantation in utero",

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 = "ACTIVATED PROTEIN-KINASE, BLASTOCYST, CULTURE-CONDITIONS, EMBRYOS LACKING, ESSENTIAL REGULATOR, FATE DECISIONS, GENE-EXPRESSION, POTENTIAL ROLE, SELF-RENEWAL, TROPHOBLAST",

author = "Jinwoo Seong and Javier Frias-Aldeguer and Viktoria Holzmann and Harunobu Kagawa and Giovanni Sestini and {Heidari Khoei}, Heidar and {Scholte Op Reimer}, Yvonne and Maarten Kip and Pradhan, {Saurabh J} and Lucas Verwegen and Judith Vivi{\'e} and Linfeng Li and Anna Alemany and Jeroen Korving and Frank Darmis and {van Oudenaarden}, Alexander and {Ten Berge}, Derk and Niels Geijsen and Rivron, {Nicolas C}",

year = "2022",

month = jul,

day = "7",

doi = "10.1016/j.stem.2022.06.002",

language = "English",

volume = "29",

pages = "1102--1118.e8",

journal = "Cell stem cell",

issn = "1934-5909",

publisher = "Cell Press",

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Seong, J, Frias-Aldeguer, J, Holzmann, V, Kagawa, H, Sestini, G, Heidari Khoei, H, Scholte Op Reimer, Y, Kip, M, Pradhan, SJ, Verwegen, L, Vivié, J, Li, L, Alemany, A, Korving, J, Darmis, F, van Oudenaarden, A, Ten Berge, D, Geijsen, N & Rivron, NC 2022, 'Epiblast inducers capture mouse trophectoderm stem cells in vitro and pattern blastoids for implantation in utero', Cell stem cell, vol. 29, no. 7, pp. 1102-1118.e8. https://doi.org/10.1016/j.stem.2022.06.002

TY - JOUR

T1 - Epiblast inducers capture mouse trophectoderm stem cells in vitro and pattern blastoids for implantation in utero

AU - Seong, Jinwoo

AU - Frias-Aldeguer, Javier

AU - Holzmann, Viktoria

AU - Kagawa, Harunobu

AU - Sestini, Giovanni

AU - Heidari Khoei, Heidar

AU - Scholte Op Reimer, Yvonne

AU - Kip, Maarten

AU - Pradhan, Saurabh J

AU - Verwegen, Lucas

AU - Vivié, Judith

AU - Li, Linfeng

AU - Alemany, Anna

AU - Korving, Jeroen

AU - Darmis, Frank

AU - van Oudenaarden, Alexander

AU - Ten Berge, Derk

AU - Geijsen, Niels

AU - Rivron, Nicolas C

PY - 2022/7/7

Y1 - 2022/7/7

N2 - 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.

AB - 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.

KW - ACTIVATED PROTEIN-KINASE

KW - BLASTOCYST

KW - CULTURE-CONDITIONS

KW - EMBRYOS LACKING

KW - ESSENTIAL REGULATOR

KW - FATE DECISIONS

KW - GENE-EXPRESSION

KW - POTENTIAL ROLE

KW - SELF-RENEWAL

KW - TROPHOBLAST

U2 - 10.1016/j.stem.2022.06.002

DO - 10.1016/j.stem.2022.06.002

M3 - Article

C2 - 35803228

SN - 1934-5909

VL - 29

SP - 1102-1118.e8

JO - Cell stem cell

JF - Cell stem cell

IS - 7

ER -