RT Journal Article
T1 Transient exposure to miR-203 enhances the differentiation capacity of established pluripotent stem cells
A1 Salazar Roa, María
A1 Trakala, Marianna
A1 Álvarez-Fernández, Mónica
A1 Valdés-Mora, Fátima
A1 Zhong, Cuiqing
A1 Muñoz, Jaime
A1 Yu, Yang
A1 Peters, Timothy
A1 Graña-Castro, Osvaldo
A1 Serrano, Rosa
A1 Zapatero-Solana, Elisabet
A1 Abad, María
A1 Bueno, María José
A1 Gómez de Cedrón, Marta
A1 Fernández-Piqueras, José
A1 Serrano, Manuel
A1 Blasco, María
A1 Wang, Da-Zhi
A1 Clark, Susan
A1 Izpisua-Belmonte, Juan Carlos
A1 Ortega, Sagrario
A1 Malumbres, Marcos
AB 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.
PB EMBO Press
SN 0261-4189
YR 2020
FD 2020
LK https://hdl.handle.net/20.500.14352/95073
UL https://hdl.handle.net/20.500.14352/95073
LA eng
NO Salazar‐Roa, María, et al. «Transient Exposure to miR‐203 Enhances the Differentiation Capacity of Established Pluripotent Stem Cells». The EMBO Journal, vol. 39, n.o 16, agosto de 2020, p. e104324. https://doi.org/10.15252/embj.2019104324.
NO M.S.R. was supported by the Asociación Española contra el Cáncer (AECC; 2012 AIOA120833SALA and 2018 INVES18005SALA) and a Juan de la Cierva contract from the Ministry of Science, Innovation and Universities (MICIU). M.T. was supported by Fundación La Caixa. M.A.F. was supported by MICIU (SAF2014‐60442‐JIN). J.F.P. was funded by MICIU (RTI2018‐093330‐B/FEDER‐EU), Ramón Areces Foundation (CIVP19S7917), CAM (B2017/BMD‐3778), and AECC (2018, PROYE18054PIRI). F.V.M was supported by the National Breast Cancer Foundation/Cure Cancer Australia Foundation Postdoctoral Training Fellow. Work in S.J.C laboratory was supported by the National Health and Medical Research Council (NHMRC 1063560). M.A.B. laboratory is funded by SAF2013‐45111‐R from MICIU, Fundación Botín and Banco Santander, and Worldwide Cancer Research (WCR16‐1177). Work in S.O. laboratory was funded by MICIU grant (SAF2013‐44866‐R). Work in the M.M. laboratory was supported by grants from the MICIU (RTI2018‐095582‐B‐I00, RED2018‐102723‐T, and SAF2017‐92729‐EXP), and the iLUNG Programme (B2017/BMD‐3884) from the Comunidad de Madrid. The CNIO is a Severo Ochoa Centers of Excellence (MICIU award SEV‐2015‐0510).
NO Ministerio de Ciencia, Innovación y Universidades (España)
NO Comunidad de Madrid
NO Asociación Española contra el Cáncer
NO Fundación La Caixa
NO Fundación Botín
NO National Breast Cancer Foundation (Australia)
NO National Health and Medical Research Council  (Australia)
NO Worldwide Cancer Research
NO European Commission
DS Docta Complutense
RD 6 abr 2025