Large scale production of human blastoids amenable to modeling blastocyst development and maternal-fetal crosstalk

Yu, L.; Ezashi, T.; Wei, Y.; Duan, J.; Logsdon, D.; Zhan, L.; Nahar, A.; Arteaga, C. P.; Liu, L.; Stobbe, C.; Katz-Jaffe, M.; Schoolcraft, W. B.; Wang, L.; Tan, T.; Hon, G. C.; Yuan, Y.; Wu, J.

doi:10.1101/2022.09.14.507946

bioRxiv · 10.1101/2022.09.14.507946

Large scale production of human blastoids amenable to modeling blastocyst development and maternal-fetal crosstalk

Yu, L.·Ezashi, T.·Wei, Y.·Duan, J.·Logsdon, D.·Zhan, L.·Nahar, A.·Arteaga, C. P.·Liu, L.·Stobbe, C.·Katz-Jaffe, M.·Schoolcraft, W. B.·Wang, L.·Tan, T.·Hon, G. C.·Yuan, Y.·Wu, J.

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Abstract

Recent advances in human blastoids generated from naive pluripotent stem cells have opened a new avenue for modelling early human development and implantation. Despite the success, however, existing protocols have several limitations, e.g., the use of custom-built microwell arrays impedes wide adoption by the research community, and mass production of human blastoids is hampered by low-output or low-efficiency methods. To address these issues, here we developed an optimized protocol based on commercially available microwell plates, which enabled efficient generation of high-fidelity human blastoids at a large scale. Leveraging on the improved protocol, we identified MAPK. PI3K/AKT and mTOR signaling pathways were activated in both blastoids and blastocyst, and discovered endometrial stromal effects in promoting trophoblast cell survival, proliferation and syncytialization during extended co-culture with blastoids. Our optimized protocol will facilitate broader use of human blastoids as an accessible, perturbable, scalable, tractable, and ethical model for human blastocysts.

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Yu, L., Ezashi, T., Wei, Y., Duan, J., Logsdon, D., Zhan, L., Nahar, A., Arteaga, C. P., Liu, L., Stobbe, C., Katz-Jaffe, M., Schoolcraft, W. B., Wang, L., Tan, T., Hon, G. C., Yuan, Y., Wu, J.. 2022-09-17. Large scale production of human blastoids amenable to modeling blastocyst development and maternal-fetal crosstalk. https://doi.org/10.1101/2022.09.14.507946

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