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Human blastoids model blastocyst development and implantation

Author

Listed:
  • Harunobu Kagawa

    (Vienna BioCenter (VBC))

  • Alok Javali

    (Vienna BioCenter (VBC))

  • Heidar Heidari Khoei

    (Vienna BioCenter (VBC))

  • Theresa Maria Sommer

    (Vienna BioCenter (VBC))

  • Giovanni Sestini

    (Vienna BioCenter (VBC))

  • Maria Novatchkova

    (Vienna BioCenter (VBC)
    Vienna Biocenter)

  • Yvonne Scholte op Reimer

    (Vienna BioCenter (VBC))

  • Gaël Castel

    (Université de Nantes, CHU Nantes, INSERM, Centre de Recherche en Transplantation et Immunologie)

  • Alexandre Bruneau

    (Université de Nantes, CHU Nantes, INSERM, Centre de Recherche en Transplantation et Immunologie)

  • Nina Maenhoudt

    (KU Leuven, (University of Leuven))

  • Jenna Lammers

    (Université de Nantes, CHU Nantes, INSERM, Centre de Recherche en Transplantation et Immunologie
    CHU Nantes, Service de Biologie de la Reproduction)

  • Sophie Loubersac

    (Université de Nantes, CHU Nantes, INSERM, Centre de Recherche en Transplantation et Immunologie
    CHU Nantes, Service de Biologie de la Reproduction)

  • Thomas Freour

    (Université de Nantes, CHU Nantes, INSERM, Centre de Recherche en Transplantation et Immunologie
    CHU Nantes, Service de Biologie de la Reproduction)

  • Hugo Vankelecom

    (KU Leuven, (University of Leuven))

  • Laurent David

    (Université de Nantes, CHU Nantes, INSERM, Centre de Recherche en Transplantation et Immunologie
    Université de Nantes, CHU Nantes, INSERM, CNRS, SFR Santé, FED 4203, INSERM UMS 016)

  • Nicolas Rivron

    (Vienna BioCenter (VBC))

Abstract

One week after fertilization, human embryos implant into the uterus. This event requires the embryo to form a blastocyst consisting of a sphere encircling a cavity lodging the embryo proper. Stem cells can form a blastocyst model that we called a blastoid1. Here we show that naive human pluripotent stem cells cultured in PXGL medium2 and triply inhibited for the Hippo, TGF-β and ERK pathways efficiently (with more than 70% efficiency) form blastoids generating blastocyst-stage analogues of the three founding lineages (more than 97% trophectoderm, epiblast and primitive endoderm) according to the sequence and timing of blastocyst development. Blastoids spontaneously form the first axis, and we observe that the epiblast induces the local maturation of the polar trophectoderm, thereby endowing blastoids with the capacity to directionally attach to hormonally stimulated endometrial cells, as during implantation. Thus, we propose that such a human blastoid is a faithful, scalable and ethical model for investigating human implantation and development3,4.

Suggested Citation

  • Harunobu Kagawa & Alok Javali & Heidar Heidari Khoei & Theresa Maria Sommer & Giovanni Sestini & Maria Novatchkova & Yvonne Scholte op Reimer & Gaël Castel & Alexandre Bruneau & Nina Maenhoudt & Jenna, 2022. "Human blastoids model blastocyst development and implantation," Nature, Nature, vol. 601(7894), pages 600-605, January.
    • Handle: RePEc:nat:nature:v:601:y:2022:i:7894:d:10.1038_s41586-021-04267-8
    DOI: 10.1038/s41586-021-04267-8
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    Citations

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    Cited by:

    1. Xavier Santamaria & Beatriz Roson & Raul Perez-Moraga & Nandakumar Venkatesan & Maria Pardo-Figuerez & Javier Gonzalez-Fernandez & Jaime Llera-Oyola & Estefania Fernández & Inmaculada Moreno & Andres , 2023. "Decoding the endometrial niche of Asherman’s Syndrome at single-cell resolution," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Albert Stuart Reece & Gary Kenneth Hulse, 2022. "Epigenomic and Other Evidence for Cannabis-Induced Aging Contextualized in a Synthetic Epidemiologic Overview of Cannabinoid-Related Teratogenesis and Cannabinoid-Related Carcinogenesis," IJERPH, MDPI, vol. 19(24), pages 1-57, December.
    3. Denis Torre & Nancy J. Francoeur & Yael Kalma & Ilana Gross Carmel & Betsaida S. Melo & Gintaras Deikus & Kimaada Allette & Ron Flohr & Maya Fridrikh & Konstantinos Vlachos & Kent Madrid & Hardik Shah, 2023. "Isoform-resolved transcriptome of the human preimplantation embryo," Nature Communications, Nature, vol. 14(1), pages 1-23, December.
    4. Yueli Yang & Wenqi Jia & Zhiwei Luo & Yunpan Li & Hao Liu & Lixin Fu & Jinxiu Li & Yu Jiang & Junjian Lai & Haiwei Li & Babangida Jabir Saeed & Yi Zou & Yuan Lv & Liang Wu & Ting Zhou & Yongli Shan & , 2024. "VGLL1 cooperates with TEAD4 to control human trophectoderm lineage specification," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    5. 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.

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