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Blastocyst-like structures generated from human pluripotent stem cells

Author

Listed:
  • Leqian Yu

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Yulei Wei

    (University of Texas Southwestern Medical Center
    Wuyi University
    International Healthcare Innovation Institute)

  • Jialei Duan

    (University of Texas Southwestern Medical Center)

  • Daniel A. Schmitz

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Masahiro Sakurai

    (University of Texas Southwestern Medical Center)

  • Lei Wang

    (University of Texas Southwestern Medical Center)

  • Kunhua Wang

    (First Affiliated Hospital of Kunming Medical University, Kunming Medical University)

  • Shuhua Zhao

    (First Affiliated Hospital of Kunming Medical University, Kunming Medical University)

  • Gary C. Hon

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

  • Jun Wu

    (University of Texas Southwestern Medical Center
    University of Texas Southwestern Medical Center)

Abstract

Limited access to embryos has hampered the study of human embryogenesis and disorders that occur during early pregnancy. Human pluripotent stem cells provide an alternative means to study human development in a dish1–7. Recent advances in partial embryo models derived from human pluripotent stem cells have enabled human development to be examined at early post-implantation stages8–14. However, models of the pre-implantation human blastocyst are lacking. Starting from naive human pluripotent stem cells, here we developed an effective three-dimensional culture strategy with successive lineage differentiation and self-organization to generate blastocyst-like structures in vitro. These structures—which we term ‘human blastoids’—resemble human blastocysts in terms of their morphology, size, cell number, and composition and allocation of different cell lineages. Single-cell RNA-sequencing analyses also reveal the transcriptomic similarity of blastoids to blastocysts. Human blastoids are amenable to embryonic and extra-embryonic stem cell derivation and can further develop into peri-implantation embryo-like structures in vitro. Using chemical perturbations, we show that specific isozymes of protein kinase C have a critical function in the formation of the blastoid cavity. Human blastoids provide a readily accessible, scalable, versatile and perturbable alternative to blastocysts for studying early human development, understanding early pregnancy loss and gaining insights into early developmental defects.

Suggested Citation

  • Leqian Yu & Yulei Wei & Jialei Duan & Daniel A. Schmitz & Masahiro Sakurai & Lei Wang & Kunhua Wang & Shuhua Zhao & Gary C. Hon & Jun Wu, 2021. "Blastocyst-like structures generated from human pluripotent stem cells," Nature, Nature, vol. 591(7851), pages 620-626, March.
  • Handle: RePEc:nat:nature:v:591:y:2021:i:7851:d:10.1038_s41586-021-03356-y
    DOI: 10.1038/s41586-021-03356-y
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    Cited by:

    1. 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.
    2. 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.
    3. 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.

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