Human blastocysts are comprised of the first three cell lineages of the embryo: trophectoderm, epiblast and primitive endoderm, all of which are essential for early development and organ formation. However, due to ethical concerns and restricted access to human blastocysts, a comprehensive understanding of early human embryogenesis is still lacking. To bridge this knowledge gap, a reliable model system that recapitulates early stages of human embryogenesis is needed. Here we developed a three-dimensional (3D), two-step induction protocol for generating blastocyst-like structures (EPS-blastoids) from human extended pluripotent stem (EPS) cells. Morphological and single-cell transcriptomic analyses revealed that EPS-blastoids contain key cell lineages and are transcriptionally similar to human blastocysts. Furthermore, EPS-blastoids are similar with human embryos that were cultured for 8 or 10 days in vitro, in terms of embryonic structures, cell lineages and transcriptomic profiles. In conclusion, we developed a scalable system to mimic human blastocyst development, which can potentially facilitate the study of early implantation failure that induced by developmental defects at early stage.
|Original language||English (US)|
|State||Published - Sep 7 2021|
Bibliographical noteKAUST Repository Item: Exported on 2021-12-14
Acknowledged KAUST grant number(s): OSR
Acknowledgements: This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA16020700), the National Key R&D Program of China (2019YFA0110804, 2017YFA0105001, 2016YFC1000601, 2018YFA0801400, 2018YFC1003203), the National Natural Science Fundation of China (81925013, 81971381, 81771580, 81571400, 82071723, 81871162), Guangdong Basic and Applied Basic Research Foundation (2021B1515020069) and Outstanding Overseas Returnees Fund of the Peking University Third Hospital (BYSYLXHG2019002). Work in the Li laboratory was supported by KAUST Office of Sponsored Research (OSR), under award number BAS/1/1080- 01. We thank the members of the Li lab, Jinna Xu, Baolei Yuan, Chongwei Bi, Xuan Zhou, Gerardo Ramos Mandujano, Khaled Alsayegh, Yingzi Zhang, Yeteng Tian, and KAUST Core Labs for their generous help in this research