Implantation initiation of self-assembled embryo-like structures generated using three types of mouse blastocyst-derived stem cells

Shaopeng Zhang, Tianzhi Chen, Naixin Chen, Dengfeng Gao, Bingbo Shi, Shuangbo Kong, Rachel Claire West, Ye Yuan, Minglei Zhi, Qingqing Wei, Jinzhu Xiang, Haiyuan Mu, Liang Yue, Xiaohua Lei, Xuepeng Wang, Liang Zhong, Hui Liang, Suying Cao, Juan Carlos Izpisua Belmonte, Haibin Wang and Jianyong Han ()
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Shaopeng Zhang: China Agricultural University
Tianzhi Chen: China Agricultural University
Naixin Chen: China Agricultural University
Dengfeng Gao: China Agricultural University
Bingbo Shi: China Agricultural University
Shuangbo Kong: Medical College of Xiamen University
Rachel Claire West: Colorado Center for Reproductive Medicine
Ye Yuan: Colorado Center for Reproductive Medicine
Minglei Zhi: China Agricultural University
Qingqing Wei: China Agricultural University
Jinzhu Xiang: China Agricultural University
Haiyuan Mu: China Agricultural University
Liang Yue: China Agricultural University
Xiaohua Lei: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences
Xuepeng Wang: State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences
Liang Zhong: CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences
Hui Liang: China Agricultural University
Suying Cao: Beijing University of Agriculture
Juan Carlos Izpisua Belmonte: Salk Institute for Biological Studies
Haibin Wang: Medical College of Xiamen University
Jianyong Han: China Agricultural University

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: Abstract Spatially ordered embryo-like structures self-assembled from blastocyst-derived stem cells can be generated to mimic embryogenesis in vitro. However, the assembly system and developmental potential of such structures needs to be further studied. Here, we devise a nonadherent-suspension-shaking system to generate self-assembled embryo-like structures (ETX-embryoids) using mouse embryonic, trophoblast and extra-embryonic endoderm stem cells. When cultured together, the three cell types aggregate and sort into lineage-specific compartments. Signaling among these compartments results in molecular and morphogenic events that closely mimic those observed in wild-type embryos. These ETX-embryoids exhibit lumenogenesis, asymmetric patterns of gene expression for markers of mesoderm and primordial germ cell precursors, and formation of anterior visceral endoderm-like tissues. After transplantation into the pseudopregnant mouse uterus, ETX-embryoids efficiently initiate implantation and trigger the formation of decidual tissues. The ability of the three cell types to self-assemble into an embryo-like structure in vitro provides a powerful model system for studying embryogenesis.

Date: 2019
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DOI: 10.1038/s41467-019-08378-9

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