Nuclear miRNA-mediated gene silencing dependent on Argonaute proteins is required for embryonic stem cell differentiation [1_Differentiation_rna_seq]

Here, we show that embryonic stem cells (ESCs) and muscle stem cells contain high levels of nuclear AGO proteins and that in ESCs nuclear AGO2 protein activity is sufficient to allow for differentiation. Transcriptome-wide mapping of binding sites at nucleotide resolution revealed that nuclear AGO2 expands its target sequence repertoire in a miRNA-dependent manner to include intronic sequences to induce post-transcriptional gene silencing LIF withdrawal and ESC differentiation for 6 days with WT ESC and ESC expressing NLS-AGO2