Researchers discover L1td1 maintains stem cell pluripotency by degrading totipotency-associated RNAs

A new study 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 (PSCs) from reverting to a totipotent state. The research demonstrates that loss of L1td1 triggers the reactivation of totipotency-associated genes and endogenous retroviruses (ERVs), prompting cells to spontaneously regress to a totipotent-like (or 2-cell-like) state that mirrors the earliest stages of embryogenesis. Notably, the study identifies L1td1 as a key post-transcriptional regulator that suppresses endogenous viral elements to sustain pluripotency.