Journal
NATIONAL SCIENCE REVIEW
Volume 10, Issue 9, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nsr/nwad173
Keywords
SCNT; reprogramming; implantation; Wnt; naive pluripotency; primed pluripotency; epiblast; single-cell RNA-seq; epigenetic barrier
Categories
Ask authors/readers for more resources
Somatic cell nuclear transfer (SCNT) can reprogram differentiated somatic cells into totipotency, but most SCNT blastocysts are arrested at the peri-implantation stage. In this study, a 3D in vitro culture system for SCNT peri-implantation embryos was developed, and it was found that persistent Wnt signals blocked the pluripotency transition of epiblasts, leading to defects in epiblast transformation events and implantation failure. Manipulating Wnt signals improved the cloning efficiency and enhanced the lineage developmental trajectories of SCNT blastocysts during peri-implantation development.
Somatic cell nuclear transfer (SCNT) can reprogram differentiated somatic cells into totipotency. Although pre-implantation development of SCNT embryos has greatly improved, most SCNT blastocysts are still arrested at the peri-implantation stage, and the underlying mechanism remains elusive. Here, we develop a 3D in vitro culture system for SCNT peri-implantation embryos and discover that persistent Wnt signals block the naive-to-primed pluripotency transition of epiblasts with aberrant H3K27me3 occupancy, which in turn leads to defects in epiblast transformation events and subsequent implantation failure. Strikingly, manipulating Wnt signals can attenuate the pluripotency transition and H3K27me3 deposition defects in epiblasts and achieve up to a 9-fold increase in cloning efficiency. Finally, single-cell RNA-seq analysis reveals that Wnt inhibition markedly enhances the lineage developmental trajectories of SCNT blastocysts during peri-implantation development. Overall, these findings reveal diminished potentials of SCNT blastocysts for lineage specification and validate a critical peri-implantation barrier for SCNT embryos.
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