Transient exposure to miR-203 enhances the differentiation capacity of established pluripotent stem cells.
EMBO J
; 39(16): e104324, 2020 08 17.
Article
en En
| MEDLINE
| ID: mdl-32614092
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.
Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Diferenciación Celular
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Metilación de ADN
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MicroARNs
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Epigénesis Genética
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Células Madre Pluripotentes Inducidas
Límite:
Animals
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Humans
Idioma:
En
Revista:
EMBO J
Año:
2020
Tipo del documento:
Article
País de afiliación:
España