A developmental landscape of 3D-cultured human pre-gastrulation embryos

Lifeng Xiang, Yu Yin, Yun Zheng, Yanping Ma, Yonggang Li, Zhigang Zhao, Junqiang Guo, Zongyong Ai, Yuyu Niu, Kui Duan, Jingjing He, Shuchao Ren, Dan Wu, Yun Bai, Zhouchun Shang, Xi Dai, Weizhi Ji () and Tianqing Li ()
Additional contact information
Lifeng Xiang: Kunming University of Science and Technology
Yu Yin: Kunming University of Science and Technology
Yun Zheng: Kunming University of Science and Technology
Yanping Ma: The First People’s Hospital of Yunnan Province
Yonggang Li: The First People’s Hospital of Yunnan Province
Zhigang Zhao: Kunming University of Science and Technology
Junqiang Guo: Kunming University of Science and Technology
Zongyong Ai: Kunming University of Science and Technology
Yuyu Niu: Kunming University of Science and Technology
Kui Duan: Kunming University of Science and Technology
Jingjing He: Kunming University of Science and Technology
Shuchao Ren: Kunming University of Science and Technology
Dan Wu: Kunming University of Science and Technology
Yun Bai: The First People’s Hospital of Yunnan Province
Zhouchun Shang: BGI-Shenzhen
Xi Dai: BGI-Shenzhen
Weizhi Ji: Kunming University of Science and Technology
Tianqing Li: Kunming University of Science and Technology

Nature, 2020, vol. 577, issue 7791, 537-542

Abstract: Abstract Our understanding of how human embryos develop before gastrulation, including spatial self-organization and cell type ontogeny, remains limited by available two-dimensional technological platforms1,2 that do not recapitulate the in vivo conditions3–5. Here we report a three-dimensional (3D) blastocyst-culture system that enables human blastocyst development up to the primitive streak anlage stage. These 3D embryos mimic developmental landmarks and 3D architectures in vivo, including the embryonic disc, amnion, basement membrane, primary and primate unique secondary yolk sac, formation of anterior–posterior polarity and primitive streak anlage. Using single-cell transcriptome profiling, we delineate ontology and regulatory networks that underlie the segregation of epiblast, primitive endoderm and trophoblast. Compared with epiblasts, the amniotic epithelium shows unique and characteristic phenotypes. After implantation, specific pathways and transcription factors trigger the differentiation of cytotrophoblasts, extravillous cytotrophoblasts and syncytiotrophoblasts. Epiblasts undergo a transition to pluripotency upon implantation, and the transcriptome of these cells is maintained until the generation of the primitive streak anlage. These developmental processes are driven by different pluripotency factors. Together, findings from our 3D-culture approach help to determine the molecular and morphogenetic developmental landscape that occurs during human embryogenesis.

Date: 2020
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DOI: 10.1038/s41586-019-1875-y

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