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

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

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

Author: Kuisheng LIU ¹ ; Xiaocui XU ¹ ; Dandan BAI ¹ ; Yanhe LI ¹ ; Yalin ZHANG ¹ ; Yanping JIA ¹ ; Mingyue GUO ¹ ; Xiaoxiao HAN ¹ ; Yingdong LIU ¹ ; Yifan SHENG ¹ ; Xiaochen KOU ¹ ; Yanhong ZHAO ¹ ; Jiqing YIN ¹ ; Sheng LIU ¹ ; Jiayu CHEN ¹ ; Hong WANG ¹ ; Yixuan WANG ¹ ; Wenqiang LIU ¹ ; Shaorong GAO ¹
Author Information

1. Shanghai Key Laboratory of Maternal Fetal Medicine, Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Frontier Science Center for Stem Cell Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.
Publication Type:Research Support, Non-U.S. Gov't
Keywords: Gata6; EPS cells; blastoid; primitive endoderm (PrE); trophectoderm (TE)
MeSH: Pregnancy; Female; Animals; Mice; Tetraploidy; Blastocyst; Embryo, Mammalian; Cell Differentiation; Embryonic Development
From: Protein & Cell 2023;14(4):262-278
CountryChina
Language:English
Abstract: 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.