OTX2 inhibits human pluripotent stem cell reprogramming toward 8-cell-like and morula-like states.

ABSTRACT: In human embryos, major zygotic genome activation (ZGA) initiates at the 8-cell (8C) blastomere stage, marking the start of the ontogenesis program. Recent advancements have shown that primed human pluripotent stem cells (hPSCs) can be reprogrammed to 8C-like cells (8CLCs) with totipotent characteristics in vitro. However, the key regulators driving this transition remain largely unexplored. In this study, we identify OTX2 as a key factor that establishes a repressive barrier to the induction of 8CLCs from primed hPSCs. Our findings reveal that OTX2 deletion greatly enhances the generation of TPRX1-EGFP⁺ 8CLCs, which closely resemble the transcriptomic profiles and epigenetic landscape of 8C/morula embryos. Notably, these OTX2-deleted 8CLCs exhibit improved bidirectional differe

SUBMITTER: Kong X 

PROVIDER: S-EPMC12909843 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature