<i>Dicer</i>, a new regulator of pluripotency exit and <scp>LINE</scp>‐1 elements in mouse embryonic stem cells

Abstract

A gene regulation network orchestrates processes ensuring the maintenance of cellular identity and genome integrity. Small RNAs generated by the RNAse III DICER have emerged as central players in this network. Moreover, deletion of <i>Dicer</i> in mice leads to early embryonic lethality. To better understand the underlying mechanisms leading to this phenotype, we generated <i>Dicer</i>-deficient mouse embryonic stem cells (mESCs). Their detailed characterization revealed an impaired differentiation potential, and incapacity to exit from the pluripotency state. We also observed a strong accumulation of LINE-1 (L1s) transcripts, which was translated at protein level and led to an increased L1s retrotransposition. Our findings reveal <i>Dicer</i> as a new essential player that sustains mESCs self-renewal and genome integrity by controlling L1s regulation.