Journal
NATURE
Volume 605, Issue 7909, Pages 315-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41586-022-04625-0
Keywords
-
Categories
Funding
- National Key Research and Development Program of China [2018YFA0106903, 2016YFA0100102]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16030502]
- National Natural Science Foundation of China [U20A2015, 31900466, 32150410348, 32070861, 31950410553]
- Guangdong Provincial Key Laboratory of Genome Read and Write [2017B030301011]
- Guangdong Basic and Applied Basic Research Foundation [2021A1515110180]
- Guangzhou Science and Technology Foundation [2021000122]
- CAS-TWAS President's PhD Fellowship
- CAS President's International Fellowship Initiative (PIFI) [2020FSB0002]
Ask authors/readers for more resources
This study presents a method for producing eight-cell-like cells (8CLCs) from human pluripotent stem cells, and identifies key molecular events and gene networks associated with this conversion through single-cell analysis. The experiments demonstrate the important roles of DPPA3 and TPRX1 in this process. This research provides a resource to uncover the molecular process of early human embryogenesis.
After fertilization, the quiescent zygote experiences a burst of genome activation that initiates a short-lived totipotent state. Understanding the process of totipotency in human cells would have broad applications. However, in contrast to in mice(1,2), demonstration of the time of zygotic genome activation or the eight-cell (8C) stage in in vitro cultured human cells has not yet been reported, and the study of embryos is limited by ethical and practical considerations. Here we describe a transgene-free, rapid and controllable method for producing 8C-like cells (8CLCs) from human pluripotent stem cells. Single-cell analysis identified key molecular events and gene networks associated with this conversion. Loss-of-function experiments identified fundamental roles for DPPA3, a master regulator of DNA methylation in oocytes(3), and TPRX1, a eutherian totipotent cell homeobox (ETCHbox) family transcription factor that is absent in mice(4). DPPA3 induces DNA demethylation throughout the 8CLC conversion process, whereas TPRX1 is a key executor of 8CLC gene networks. We further demonstrate that 8CLCs can produce embryonic and extraembryonic lineages in vitro or in vivo in the form of blastoids 5 and complex teratomas. Our approach provides a resource to uncover the molecular process of early human embryogenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available