Blastocyst-like structures generated from human pluripotent stem cells

Leqian Yu, Yulei Wei, Jialei Duan, Daniel A. Schmitz, Masahiro Sakurai, Lei Wang, Kunhua Wang, Shuhua Zhao, Gary C. Hon () and Jun Wu ()
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Leqian Yu: University of Texas Southwestern Medical Center
Yulei Wei: University of Texas Southwestern Medical Center
Jialei Duan: University of Texas Southwestern Medical Center
Daniel A. Schmitz: 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
Jun Wu: University of Texas Southwestern Medical Center

Nature, 2021, vol. 591, issue 7851, 620-626

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41586-021-03356-y

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