biostudies-literatureUnknown8(1)Wang BThe human silencing hub (HUSH) maintains the genome integrity by silencing invasive genetic elements. However, despite essential roles of the HUSH complex during early embryonic development, the function of the complex in the maintenance of pluripotency is mostly unknown. Here, using CRISPR-based genome editing, we demonstrate that in mouse embryonic stem cells (mESCs), deficiency of HUSH core members MPP8 or TASOR, but not PPHLN1, triggers alteration of colony morphology, and mild defect in exit from pluripotency. Importantly, Mpp8/Tasor double mutants are locked in pluripotent state even upon differentiation stimuli. We further demonstrate that these phenotypes are accompanied by decreased expression of adhesion-related genes. Strikingly, the abnormalities observed in Mpp8/Tasor-null mESCommunications biology1679https://www.ebi.ac.uk/biostudies/studies/S-EPMC12647722biostudies-literatureThe HUSH complex facilitates the exit of pluripotency.PMC12647722Xu LXia YLing SQi MWang BLiao HQin JJiang XDong LSun YXu YfalseThe HUSH complex facilitates the exit of pluripotency.The human silencing hub (HUSH) maintains the genome integrity by silencing invasive genetic elements. However, despite essential roles of the HUSH complex during early embryonic development, the function of the complex in the maintenance of pluripotency is mostly unknown. Here, using CRISPR-based genome editing, we demonstrate that in mouse embryonic stem cells (mESCs), deficiency of HUSH core members MPP8 or TASOR, but not PPHLN1, triggers alteration of colony morphology, and mild defect in exit from pluripotency. Importantly, Mpp8/Tasor double mutants are locked in pluripotent state even upon differentiation stimuli. We further demonstrate that these phenotypes are accompanied by decreased expression of adhesion-related genes. Strikingly, the abnormalities observed in Mpp8/Tasor-null mES2025-01-01T00:00:00Z2025 Nov2026-06-05T16:44:33.645Z2026-05-18T03:13:08.455ZS-EPMC126477224129101210.1038/s42003-025-09080-x