2026-07-21T14:26:46Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/176732024-11-29T23:25:01Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc de la Rosa, Sergio author Del Mar Rigual, María author Vargiu, Pierfrancesco author Ortega Jimenez, Sagrario author Djouder, Nabil author 2024-01-26 The smooth and precise transition from totipotency to pluripotency is a key process in embryonic development, generating pluripotent stem cells capable of forming all cell types. While endogenous retroviruses (ERVs) are essential for early development, their precise roles in this transition remains mysterious. Using cutting-edge genetic and biochemical techniques in mice, we identify MERVL-gag, a retroviral protein, as a crucial modulator of pluripotent factors OCT4 and SOX2 during lineage specification. MERVL-gag tightly operates with URI, a prefoldin protein that concurs with pluripotency bias in mouse blastomeres, and which is indeed required for totipotency-to-pluripotency transition. Accordingly, URI loss promotes a stable totipotent-like state and embryo arrest at 2C stage. Mechanistically, URI binds and shields OCT4 and SOX2 from proteasome degradation, while MERVL-gag displaces URI from pluripotent factor interaction, causing their degradation. Our findings reveal the symbiotic coevolution of ERVs with their host cells to ensure the smooth and timely progression of early embryo development. Sci Adv . 2024 ;10(4):eadk9394. 10.1126/sciadv.adk9394 2375-2548 Science advances 38266080 http://hdl.handle.net/20.500.12105/17673 Endogenous retroviruses shape pluripotency specification in mouse embryos.