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oai:repisalud.isciii.es:20.500.12105/181832025-05-29T18:44:20Zcom_20.500.12105_2173com_20.500.12105_2051col_20.500.12105_19597

00925njm 22002777a 4500 dc Salazar-Roa, María author Trakala, Marianna author Álvarez-Fernández, Mónica author Valdés-Mora, Fátima author Zhong, Cuiqing author Muñoz, Jaime author Yu, Yang author Peters, Timothy J author Graña Castro, Osvaldo author Serrano, Rosa author Zapatero-Solana, Elisabet author Abad, María author Bueno, María José author Gómez de Cedrón, Marta author Fernández-Piqueras, José author Serrano, Manuel author Blasco, MA author Wang, Da-Zhi author Clark, Susan J author Izpisua-Belmonte, Juan Carlos author Ortega Jimenez, Sagrario author Malumbres, Marcos author 2020-08-17 Full differentiation potential along with self-renewal capacity is a major property of pluripotent stem cells (PSCs). However, the differentiation capacity frequently decreases during expansion of PSCs in vitro. We show here that transient exposure to a single microRNA, expressed at early stages during normal development, improves the differentiation capacity of already-established murine and human PSCs. Short exposure to miR-203 in PSCs (miPSCs) induces a transient expression of 2C markers that later results in expanded differentiation potency to multiple lineages, as well as improved efficiency in tetraploid complementation and human-mouse interspecies chimerism assays. Mechanistically, these effects are at least partially mediated by direct repression of de novo DNA methyltransferases Dnmt3a and Dnmt3b, leading to transient and reversible erasure of DNA methylation. These data support the use of transient exposure to miR-203 as a versatile method to reset the epigenetic memory in PSCs, and improve their effectiveness in regenerative medicine. EMBO J . 2020;39(16):e104324. 10.15252/embj.2019104324 1460-2075 The EMBO journal 32614092 http://hdl.handle.net/20.500.12105/18183 Transient exposure to miR-203 enhances the differentiation capacity of established pluripotent stem cells.