Bilineage Embryo-like Structure from EPS Cells Can Produce Live Mice with Tetraploid Trophectoderm

Overview

Journal Protein Cell

Publisher Oxford University Press

Specialties Biochemistry
Cell Biology

Date 2023 Apr 21

PMID 37084236

Authors

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

Affiliations

Soon will be listed here.

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.

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