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bioRxiv · 10.1101/2023.06.15.545180

Dissecting peri-implantation development using cultured human embryos and embryo-like assembloids

Ai, Z.·Niu, B.·Yin, Y.·Xiang, L.·Shi, G.·Duan, K.·Wang, S.·Hu, Y.·Zhang, C.·Rong, L.·Kong, R.·Chen, T.·Guo, Y.·Liu, W.·Li, N.·Zhao, S.·Zhu, X.·Mai, X.·Li, Y.·Wu, Z.·Zheng, Y.·Fu, J.·Ji, W.·Li, T.
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Abstract

Studies of cultured embryos have provided insights into human peri-implantation development. However, detailed knowledge of peri-implantation lineage developments as well as underlying mechanisms remain obscure. Using 3D-cultured human embryos, herein we report a complete cell atlas of the early post-implantation lineages and decipher cellular composition and gene signatures of the epiblast and hypoblast derivatives. In addition, we develop an embryo-like assembloid (E-assembloid) by assembling naive hESCs and extraembryonic cells. Using human embryos and E-assembloids, we reveal that WNT, BMP and Nodal signaling synergistically, but functionally differently, orchestrate human peri-implantation lineage development. Specially, we dissect mechanisms underlying extraembryonic mesoderm and extraembryonic endoderm specifications. Finally, an improved E-assembloid is developed to recapitulate the epiblast and hypoblast developments and tissue architectures in the pre-gastrulation human embryo. Our findings provide insights of the human peri-implantation development, and the E-assembloid offers a useful model to disentangle cellular behaviors and signaling interactions that drive human embryogenesis.

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Ai, Z., Niu, B., Yin, Y., Xiang, L., Shi, G., Duan, K., Wang, S., Hu, Y., Zhang, C., Rong, L., Kong, R., Chen, T., Guo, Y., Liu, W., Li, N., Zhao, S., Zhu, X., Mai, X., Li, Y., Wu, Z., Zheng, Y., Fu, J., Ji, W., Li, T.. 2023-06-16. Dissecting peri-implantation development using cultured human embryos and embryo-like assembloids. https://doi.org/10.1101/2023.06.15.545180

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