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

被引：15

作者：

Liu, Kuisheng ^{[1
]}

Xu, Xiaocui ^{[1
]}

Bai, Dandan ^{[1
]}

Li, Yanhe ^{[1
]}

Zhang, Yalin ^{[1
]}

Jia, Yanping ^{[1
]}

Guo, Mingyue ^{[1
]}

Han, Xiaoxiao ^{[1
]}

Liu, Yingdong ^{[1
]}

Sheng, Yifan ^{[1
]}

Kou, Xiaochen ^{[1
]}

Zhao, Yanhong ^{[1
]}

Yin, Jiqing ^{[1
]}

Liu, Sheng ^{[1
]}

Chen, Jiayu ^{[1
]}

Wang, Hong ^{[1
]}

Wang, Yixuan ^{[1
,2
]}

Liu, Wenqiang ^{[1
,3
]}

Gao, Shaorong ^{[1
,2
]}

机构：

[1] Tongji Univ, Infant Hosp,Sch Life Sci & Technol, Clin & Translat Res Ctr Shanghai Matern 1, Frontier Sci Ctr Stem Cell Res,Shanghai Key Lab Ma, Shanghai 200092, Peoples R China

[2] Tongji Univ, Shanghai East Hosp, Inst Regenerat Med,Sch Life Sci & Technol, Translat Med Ctr Stem Cell Therapy, Shanghai 200092, Peoples R China

[3] Tongji Univ, Shanghai Matern & Infant Hosp 1, Shanghai Inst Maternal Fetal Med & Gynecol Oncol, Shanghai 200092, Peoples R China

来源：

PROTEIN & CELL | 2023年 / 14卷 / 04期

基金：

中国国家自然科学基金; 中国博士后科学基金; 国家重点研发计划;

关键词：

EPS cells; blastoid; primitive endoderm (PrE); trophectoderm (TE); Gata6; BLASTOCYST-LIKE STRUCTURES; STEM-CELLS; RNA-SEQ; PRIMITIVE ENDODERM; SELF-ORGANIZATION; AXIS FORMATION; MOUSE EMBRYOS; GROUND-STATE; DERIVATION; FATE;

D O I：

10.1093/procel/pwac029

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：262 / 278

页数：17

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