Bilineage embryo-like structure from EPS cells can produce live mice with tetraploid trophectoderm.
Bilineage embryo-like structure from EPS cells can produce live mice with tetraploid trophectoderm.
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EPS细胞的双系胚胎样结构可产生具有四倍体滋养外胚层的活小鼠
DOI：
10.1093/procel/pwac029
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发表时间：
2023-04-21
期刊：
影响因子：
21.1
通讯作者：
Gao, Shaorong
中科院分区：
文献类型：
--
作者：
Liu, Kuisheng;Xu, Xiaocui;Bai, Dandan;Li, Yanhe;Zhang, Yalin;Jia, Yanping;Guo, Mingyue;Han, Xiaoxiao;Liu, Yingdong;Sheng, Yifan;Kou, Xiaochen;Zhao, Yanhong;Yin, Jiqing;Liu, Sheng;Chen, Jiayu;Wang, Hong;Wang, Yixuan;Liu, Wenqiang;Gao, Shaorong
扩展多能干细胞（EPS）的自组织囊胚在研究胚胎移植后发育及相关疾病方面具有巨大的潜力。然而，eps -囊胚移植后发育能力有限，阻碍了其进一步应用。本研究通过单细胞转录组学分析发现，eps -囊胚的“滋养外胚层（TE）样结构”主要由原始内胚层（PrE）相关细胞组成，而非TE相关细胞。我们进一步在EPS细胞培养中发现PrE-like细胞有助于形成具有te样结构的囊胚。通过抑制MEK信号或敲除Gata6在EPS细胞中抑制PrE细胞分化可显著抑制EPS囊胚的形成。此外，我们还证明了将eps衍生的双系胚胎样结构（BLES）与四倍体胚胎或四倍体TE细胞结合重建的囊胚样结构可以正常植入并发育成活胎。总之，我们的研究表明，TE的改善对于在体外使用干细胞构建功能胚胎至关重要。
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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