Transient exposure to miR-203 expands the differentiation capacity of pluripotent stem cells

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 du...

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Detalles Bibliográficos
Autores: Salazar-Roa, María, Trakala, Marianna, Álvarez Fernández, Mónica, Valdés Mora, Fátima, Zhong, Cuiqing, Muñoz, Jaime, Yu, Yang, Peters, Timothy J., Graña Castro, Osvaldo, Serrano, Rosa, Zapatero Solana, Elisabet, Abad, María Lluisa, Bueno, María José, Gómez de Cedrón, Marta, Fernández Piqueras, José, Serrano Marugán, Manuel, Blasco, María A., Wang, Da-Zhi, Clark, Susan J., Izpisúa Belmonte, Juan Carlos, Ortega, Sagrario, Malumbre, Marcos
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2020
País:España
Institución:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/167804
Acceso en línea:https://hdl.handle.net/2445/167804
Access Level:acceso abierto
Palabra clave:Micro RNAs
Cèl·lules mare
Epigenètica
MicroRNAs
Stem cells
Epigenetics
Descripción
Sumario: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 (mi PSCs) 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.

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