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Recapitulating early human development with 8C-like cells

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Item Type:Article
Title:Recapitulating early human development with 8C-like cells
Creators Name:Yu, X. and Liang, S. and Chen, M. and Yu, H. and Li, R. and Qu, Y. and Kong, X. and Guo, R. and Zheng, R. and Izsvak, Z. and Sun, C. and Yang, M. and Wang, J.
Abstract:In human embryos, major zygotic genome activation (ZGA) initiates at the eight-cell (8C) stage. Abnormal ZGA leads to developmental defects and even contributes to the failure of human blastocyst formation or implantation. An in vitro cell model mimicking human 8C blastomeres would be invaluable to understanding the mechanisms regulating key biological events during early human development. Using the non-canonical promoter of LEUTX that putatively regulates human ZGA, we developed an 8C::mCherry reporter, which specifically marks the 8C state, to isolate rare 8C-like cells (8CLCs) from human preimplantation epiblast-like stem cells. The 8CLCs express a panel of human ZGA genes and have a unique transcriptome resembling that of the human 8C embryo. Using the 8C::mCherry reporter, we further optimize the chemical-based culture condition to increase and maintain the 8CLC population. Functionally, 8CLCs can self-organize to form blastocyst-like structures. The discovery and maintenance of 8CLCs provide an opportunity to recapitulate early human development.
Keywords:Zygotic Genome Activation, 8CLC, LEUTX, ZSCAN4, DUX4, Blastoid, Preimplantation Development
Source:Cell Reports
Publisher:Cell Press / Elsevier
Page Range:110994
Date:21 June 2022
Official Publication:https://doi.org/10.1016/j.celrep.2022.110994
PubMed:View item in PubMed

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