http://english.cas.cn/newsroom/research_news/life/202602/t20260209_1150222.shtml

https://www.nature.com/articles/s41421-025-00864-3

A study at the CAS Guangzhou Institutes of Biomedicine and Health (GIBH) has found that L1td1, a protein evolutionarily co-opted from the Long interspersed nuclear element 1 (LINE1) retrotransposon, functions as a critical “gatekeeper” restricting pluripotent stem cells from reverting to a totipotent state.

The transition from totipotency to pluripotency is a fundamental event in early embryonic development, marked by the silencing of totipotent genes and specific retrotransposons activated during zygotic genome activation (ZGA). While transcriptional and epigenetic mechanisms governing this developmental restriction have been extensively investigated, the role of post-transcriptional regulation—particularly RNA decay—has remained poorly understood. To address this knowledge gap, the research team employed mouse and human PSC models and uncovered that L1td1 plays a decisive role in preventing the acquisition of totipotency. Mechanistically, L1td1 recruits the CCR4-NOT deadenylase complex to specifically target and degrade RNA transcripts essential for totipotency, including the Zscan4 gene family and ERVs such as MERVL-int and MT2_Mm.

These findings provide new theoretical insights into the evolutionary interplay between viral elements and host developmental regulation, offering potential strategies for inducing totipotency in regenerative medicine and xenogeneic organ regeneration.