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

作　　者：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 

机构地区：[1]Shanghai Key Laboratory of Matemal Fetal Medicine,Clinical and Translational Research Center of Shanghai First Matemity and Infant Hospital,Frontier Science Center for Stem Cell Research,School of Life Sciences and Technology,Tongji University,Shanghai 200092,China [2]Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine,Shanghai East Hospital,School of Life Sciences and Technology,Tongji University,Shanghai 200092,China [3]Shanghai Institute of Matermal-Fetal Medicine and Gynecologic Oncology,Shanghai First Matermity and Infant Hospital,Tongji University,Shanghai 200092,China

出　　处：《Protein & Cell》2023年第4期262-278,共17页蛋白质与细胞（英文版）

基　　金：supported by the National Key R&D Program of China(Nos.2020YFA0112500 and 2021YFA1102900);the National Natural Science Foundation of China(Nos.31721003,81630035,82022027,31871448,32000418 and 31820103009);supported by the key project of the Science and Technology of Shanghai Municipality(Nos.19JC1415300 and 21JC1405500);the Shanghai municipal medical and health discipline construction projects(No.2017ZZ02015);the China Postdoctoral Science Foundation 2021M692437 and the Fundamental Research Funds for the Central Universities.

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 EPSblastoids 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.

关 键 词：EPS cells blastoid primitive endoderm(PrE) trophectoderm(TE) Gata6 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]