TY - JOUR
T1 - Blastocyst-like structures generated from human pluripotent stem cells
AU - Yu, Leqian
AU - Wei, Yulei
AU - Duan, Jialei
AU - Schmitz, Daniel A.
AU - Sakurai, Masahiro
AU - Wang, Lei
AU - Wang, Kunhua
AU - Zhao, Shuhua
AU - Hon, Gary C.
AU - Wu, Jun
N1 - Funding Information:
Acknowledgements We thank R. Jaenisch and T. Theunissen for providing the naive WIBR3 (OCT4-2A-GFP) cells; C. Zheng for help with cell culture; L. Zhang for technical support; and all other members of the Wu laboratory for discussion and suggestions. We acknowledge the BioHPC computational infrastructure at UT Southwestern for providing high-performance computing (HPC) and storage resources that have contributed to the research results reported within this paper. We also acknowledge UT Southwestern Genomics and Microarray Core for providing next-generation sequencing services. J.W. is a Virginia Murchison Linthicum Scholar in Medical Research and funded by CPRIT (RR170076) and Hamon Center for Regenerative Science and Medicine. G.H. is supported by CPRIT (RP190451), NIH (DP2GM128203), the Welch Foundation (I-1926-20170325), the Burroughs Wellcome Fund (1019804) and the Green Center for Reproductive Biology.
Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature Limited part of Springer Nature.
PY - 2021/3/25
Y1 - 2021/3/25
N2 - 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.
AB - 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.
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U2 - 10.1038/s41586-021-03356-y
DO - 10.1038/s41586-021-03356-y
M3 - Article
C2 - 33731924
AN - SCOPUS:85103053076
VL - 591
SP - 620
EP - 626
JO - Nature
JF - Nature
SN - 0028-0836
IS - 7851
ER -