Volume 33, No 9, Sep 2023

ISSN: 1001-0602 
EISSN: 1748-7838 2018 
impact factor 17.848* 
(Clarivate Analytics, 2019)

Volume 33 Issue 9, September 2023: 661-678   |  Open Access

ORIGINAL ARTICLES

Dissecting peri-implantation development using cultured human embryos and embryo-like assembloids

Zongyong Ai^1,2,3,†,* , Baohua Niu^1,2,† , Yu Yin^1,2,3,† , Lifeng Xiang^4,† , Gaohui Shi^1,2,† , Kui Duan^1,2,3 , Sile Wang^1,2,3 , Yingjie Hu^1,2 , Chi Zhang^1,2 , Chengting Zhang^1,2,3 , Lujuan Rong^1,2 , Ruize Kong⁴ , Tingwei Chen^1,2 , Yixin Guo⁵ , Wanlu Liu⁵ , Nan Li^1,2 , Shumei Zhao^1,2,3 , Xiaoqing Zhu^1,2,3 , Xuancheng Mai⁴ , Yonggang Li⁴ , Ze Wu⁴ , Yi Zheng⁶ , Jianping Fu^6,7,8 , Weizhi Ji^1,2,3,* , Tianqing Li^1,2,3,*

¹State Key Laboratory of Primate Biomedical Research; Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming, Yunnan, China
²Yunnan Key Laboratory of Primate Biomedical Research, Kunming, Yunnan, China
³Yunnan Provincial Academy of Science and Technology, Kunming, Yunnan, China
⁴Department of Reproductive Medicine, The First People’s Hospital of Yunnan Province, Kunming, Yunnan, China
⁵Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, International Campus, Zhejiang University, Haining, Zhejiang, China
⁶Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA
⁷Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA
⁸Department of Cell & Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA
^†These authors contributed equally: Zongyong Ai, Baohua Niu, Yu Yin, Lifeng Xiang, Gaohui Shi
Correspondence: Zongyong Ai(aizy@lpbr.cn)Weizhi Ji(wji@lpbr.cn)Tianqing Li(litq@lpbr.cn)

Studies of cultured embryos have provided insights into human peri-implantation development. However, detailed knowledge of peri-implantation lineage development as well as underlying mechanisms remains obscure. Using 3D-cultured human embryos, herein we report a complete cell atlas of the early post-implantation lineages and decipher cellular composition and gene signatures of the epiblast and hypoblast derivatives. In addition, we develop an embryo-like assembloid (E-assembloid) by assembling naive hESCs and extraembryonic cells. Using human embryos and E-assembloids, we reveal that WNT, BMP and Nodal signaling pathways synergistically, but functionally differently, orchestrate human peri-implantation lineage development. Specially, we dissect mechanisms underlying extraembryonic mesoderm and extraembryonic endoderm specifications. Finally, an improved E-assembloid is developed to recapitulate the epiblast and hypoblast development and tissue architectures in the pre-gastrulation human embryo. Our findings provide insights into human peri-implantation development, and the E-assembloid offers a useful model to disentangle cellular behaviors and signaling interactions that drive human embryogenesis.

https://doi.org/10.1038/s41422-023-00846-8

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