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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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
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spelling Transient exposure to miR-203 expands the differentiation capacity of pluripotent stem cellsSalazar-Roa, MaríaTrakala, MariannaÁlvarez Fernández, MónicaValdés Mora, FátimaZhong, CuiqingMuñoz, JaimeYu, YangPeters, Timothy J.Graña Castro, OsvaldoSerrano, RosaZapatero Solana, ElisabetAbad, María LluisaBueno, María JoséGómez de Cedrón, MartaFernández Piqueras, JoséSerrano Marugán, ManuelBlasco, María A.Wang, Da-ZhiClark, Susan J.Izpisúa Belmonte, Juan CarlosOrtega, SagrarioMalumbre, MarcosMicro RNAsCèl·lules mareEpigenèticaMicroRNAsStem cellsEpigeneticsFull 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.EMBO Press2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/167804Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a: https://doi.org/10.15252/embj.2019104324The EMBO Journal, 2020, e104324https://doi.org/10.15252/embj.2019104324(c) Salazar Roa et al., 2020info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/1678042026-05-27T06:46:51Z
dc.title.none.fl_str_mv Transient exposure to miR-203 expands the differentiation capacity of pluripotent stem cells
title Transient exposure to miR-203 expands the differentiation capacity of pluripotent stem cells
spellingShingle Transient exposure to miR-203 expands the differentiation capacity of pluripotent stem cells
Salazar-Roa, María
Micro RNAs
Cèl·lules mare
Epigenètica
MicroRNAs
Stem cells
Epigenetics
title_short Transient exposure to miR-203 expands the differentiation capacity of pluripotent stem cells
title_full Transient exposure to miR-203 expands the differentiation capacity of pluripotent stem cells
title_fullStr Transient exposure to miR-203 expands the differentiation capacity of pluripotent stem cells
title_full_unstemmed Transient exposure to miR-203 expands the differentiation capacity of pluripotent stem cells
title_sort Transient exposure to miR-203 expands the differentiation capacity of pluripotent stem cells
dc.creator.none.fl_str_mv 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
author Salazar-Roa, María
author_facet 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
author_role author
author2 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
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Micro RNAs
Cèl·lules mare
Epigenètica
MicroRNAs
Stem cells
Epigenetics
topic Micro RNAs
Cèl·lules mare
Epigenètica
MicroRNAs
Stem cells
Epigenetics
description 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.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/167804
url https://hdl.handle.net/2445/167804
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a: https://doi.org/10.15252/embj.2019104324
The EMBO Journal, 2020, e104324
https://doi.org/10.15252/embj.2019104324
dc.rights.none.fl_str_mv (c) Salazar Roa et al., 2020
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Salazar Roa et al., 2020
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv EMBO Press
publisher.none.fl_str_mv EMBO Press
dc.source.none.fl_str_mv Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona))
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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