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Blastocyst-like structures generated solely from stem cells

Author

Listed:
  • Nicolas C. Rivron

    (Maastricht University
    Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht)

  • Javier Frias-Aldeguer

    (Maastricht University
    Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht)

  • Erik J. Vrij

    (Maastricht University)

  • Jean-Charles Boisset

    (Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht)

  • Jeroen Korving

    (Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht)

  • Judith Vivié

    (Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht
    Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht)

  • Roman K. Truckenmüller

    (Maastricht University)

  • Alexander Oudenaarden

    (Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht)

  • Clemens A. Blitterswijk

    (Maastricht University)

  • Niels Geijsen

    (Royal Netherlands Academy of Arts and Sciences (KNAW) and UMC Utrecht
    Utrecht University)

Abstract

The blastocyst (the early mammalian embryo) forms all embryonic and extra-embryonic tissues, including the placenta. It consists of a spherical thin-walled layer, known as the trophectoderm, that surrounds a fluid-filled cavity sheltering the embryonic cells1. From mouse blastocysts, it is possible to derive both trophoblast2 and embryonic stem-cell lines3, which are in vitro analogues of the trophectoderm and embryonic compartments, respectively. Here we report that trophoblast and embryonic stem cells cooperate in vitro to form structures that morphologically and transcriptionally resemble embryonic day 3.5 blastocysts, termed blastoids. Like blastocysts, blastoids form from inductive signals that originate from the inner embryonic cells and drive the development of the outer trophectoderm. The nature and function of these signals have been largely unexplored. Genetically and physically uncoupling the embryonic and trophectoderm compartments, along with single-cell transcriptomics, reveals the extensive inventory of embryonic inductions. We specifically show that the embryonic cells maintain trophoblast proliferation and self-renewal, while fine-tuning trophoblast epithelial morphogenesis in part via a BMP4/Nodal–KLF6 axis. Although blastoids do not support the development of bona fide embryos, we demonstrate that embryonic inductions are crucial to form a trophectoderm state that robustly implants and triggers decidualization in utero. Thus, at this stage, the nascent embryo fuels trophectoderm development and implantation.

Suggested Citation

  • Nicolas C. Rivron & Javier Frias-Aldeguer & Erik J. Vrij & Jean-Charles Boisset & Jeroen Korving & Judith Vivié & Roman K. Truckenmüller & Alexander Oudenaarden & Clemens A. Blitterswijk & Niels Geijs, 2018. "Blastocyst-like structures generated solely from stem cells," Nature, Nature, vol. 557(7703), pages 106-111, May.
  • Handle: RePEc:nat:nature:v:557:y:2018:i:7703:d:10.1038_s41586-018-0051-0
    DOI: 10.1038/s41586-018-0051-0
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    Citations

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    Cited by:

    1. Bas Loo & Simone A. Den & Nuno Araújo-Gomes & Vincent Jong & Rebecca R. Snabel & Maik Schot & José M. Rivera-Arbeláez & Gert Jan C. Veenstra & Robert Passier & Tom Kamperman & Jeroen Leijten, 2023. "Mass production of lumenogenic human embryoid bodies and functional cardiospheres using in-air-generated microcapsules," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Sabine C Fischer & Elena Corujo-Simon & Joaquin Lilao-Garzon & Ernst H K Stelzer & Silvia Muñoz-Descalzo, 2020. "The transition from local to global patterns governs the differentiation of mouse blastocysts," PLOS ONE, Public Library of Science, vol. 15(5), pages 1-29, May.
    3. Anna Malkowska & Christopher Penfold & Sophie Bergmann & Thorsten E. Boroviak, 2022. "A hexa-species transcriptome atlas of mammalian embryogenesis delineates metabolic regulation across three different implantation modes," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    4. Mingyue Guo & Jinyi Wu & Chuanxin Chen & Xinggu Wang & An Gong & Wei Guan & Rowan M. Karvas & Kexin Wang & Mingwei Min & Yixuan Wang & Thorold W. Theunissen & Shaorong Gao & José C. R. Silva, 2024. "Self-renewing human naïve pluripotent stem cells dedifferentiate in 3D culture and form blastoids spontaneously," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    5. Xinyu Hu & Bob van Sluijs & Óscar García-Blay & Yury Stepanov & Koen Rietrae & Wilhelm T. S. Huck & Maike M. K. Hansen, 2024. "ARTseq-FISH reveals position-dependent differences in gene expression of micropatterned mESCs," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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