Bilineage embryo-like structure from EPS cells can produce live mice with tetraploid trophectoderm

Autor: Kuisheng Liu, Xiaocui Xu, Dandan Bai, Yanhe Li, Yalin Zhang, Yanping Jia, Mingyue Guo, Xiaoxiao Han, Yingdong Liu, Yifan Sheng, Xiaochen Kou, Yanhong Zhao, Jiqing Yin, Sheng Liu, Jiayu Chen, Hong Wang, Yixuan Wang, Wenqiang Liu, Shaorong Gao
Rok vydání: 2022
Předmět:
Zdroj: Protein & Cell.
ISSN: 1674-8018
1674-800X
DOI: 10.1093/procel/pwac029
Popis: Self-organized blastoids from extended pluripotent stem (EPS) cells possess enormous potential for investigating postimplantation embryo development and related diseases. However, the limited ability of postimplantation development of EPS-blastoids hinders its further application. In this study, single-cell transcriptomic analysis indicated that the “trophectoderm (TE)-like structure” of EPS-blastoids was primarily composed of primitive endoderm (PrE)-related cells instead of TE-related cells. We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure. Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation. Furthermore, we demonstrated that blastocyst-like structures reconstituted by combining the EPS-derived bilineage embryo-like structure (BLES) with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses. In summary, our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
Databáze: OpenAIRE
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