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

Abstract

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.

Type Journal
ISBN 1460-2075 (Electronic) 0261-4189 (Linking)
Authors Salazar-Roa, M.; Trakala, M.; Alvarez-Fernandez, M.; Valdes-Mora, F.; Zhong, C.; Munoz, J.; Yu, Y.; Peters, T. J.; Grana-Castro, O.; Serrano, R.; Zapatero-Solana, E.; Abad, M.; Bueno, M. J.; Gomez de Cedron, M.; Fernandez-Piqueras, J.; Serrano, M.; Blasco, M. A.; Wang, D. Z.; Clark, S. J.; Izpisua-Belmonte, J. C.; Ortega, S.; Malumbres, M.
Responsible Garvan Author Prof Susan Clark
Publisher Name EMBO JOURNAL
Published Date 2020-08-17
Published Volume 39
Published Issue 16
Published Pages e104324
Status Published in-print
DOI 10.15252/embj.2019104324
URL link to publisher's version https://www.ncbi.nlm.nih.gov/pubmed/32614092