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

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dc.contributor.authorSalazar-Roa, María
dc.contributor.authorTrakala, Marianna
dc.contributor.authorÁlvarez-Fernández, Mónica
dc.contributor.authorValdés-Mora, Fátima
dc.contributor.authorZhong, Cuiqing
dc.contributor.authorMuñoz, Jaime
dc.contributor.authorYu, Yang
dc.contributor.authorPeters, Timothy J
dc.contributor.authorGraña Castro, Osvaldo
dc.contributor.authorSerrano, Rosa
dc.contributor.authorZapatero-Solana, Elisabet
dc.contributor.authorAbad, María
dc.contributor.authorBueno, María José
dc.contributor.authorGómez de Cedrón, Marta
dc.contributor.authorFernández-Piqueras, José
dc.contributor.authorSerrano, Manuel
dc.contributor.authorBlasco, MA
dc.contributor.authorWang, Da-Zhi
dc.contributor.authorClark, Susan J
dc.contributor.authorIzpisua-Belmonte, Juan Carlos
dc.contributor.authorOrtega Jimenez, Sagrario
dc.contributor.authorMalumbres, Marcos
dc.contributor.funderAsociación Española Contra el Cáncer
dc.contributor.funderMinisterio de Ciencia, Innovación y Universidades (España)
dc.contributor.funderFundación La Caixa
dc.contributor.funderFundación Ramón Areces
dc.contributor.funderComunidad de Madrid (España)
dc.contributor.funderNational Breast Cancer Foundation (Australia)
dc.contributor.funderNational Health and Medical Research Council (Australia)
dc.contributor.funderWorldwide Cancer Research
dc.contributor.funderFundación Banco Santander
dc.contributor.funderMinisterio de Ciencia e Innovación. Centro de Excelencia Severo Ochoa (España)
dc.contributor.funderCure Cancer Australia
dc.date.accessioned2024-02-13T09:32:04Z
dc.date.available2024-02-13T09:32:04Z
dc.date.issued2020-08-17
dc.description.abstractFull 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.es_ES
dc.description.peerreviewedSíes_ES
dc.description.sponsorshipWe thank Maria Guirola, Sheila Rueda, and the CNIO Histopathology Unit for technical support; Carmen Gomez and Patricia Prieto for help with iPSC/ESC culture; Zsuzsanna Izsvak (Max-Delbruck-Center for Molecular Medicine, Berlin, Germany) for reagents; Marta Canamero (Pathology and Tissue Analytics, Roche Pharma, Basel, Switzerland) and Alba de Martino (Histopathology Unit, CNIO) for pathology advice; William Pu, Zhang-Peng Huang, and Kai Li (Cardiovascular Research Division, Boston Children's Hospital, USA) for help with the cardiac differentiation experiments; and Dr. Jennifer Franks (Geisel School of Medicine at Dartmouth, NH, USA) for her clarifications regarding the use of the FSQN method. We are indebted to the members of the CNIO Cell Division and Cancer laboratory for their constant support and advice. M.S.R. was supported by the Asociacion Espanola contra el Cancer (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 Fundacion La Caixa. M.A.F. was supported by MICIU (SAF2014-60442-JIN). J.F.P. was funded by MICIU (RTI2018-093330-B/FEDER-EU), Ramon 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, Fundacion Botin 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).es_ES
dc.format.number16es_ES
dc.format.pagee104324es_ES
dc.format.volume39es_ES
dc.identifier.citationEMBO J . 2020;39(16):e104324.es_ES
dc.identifier.doi10.15252/embj.2019104324es_ES
dc.identifier.e-issn1460-2075es_ES
dc.identifier.journalThe EMBO journales_ES
dc.identifier.pubmedID32614092es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/18183
dc.language.isoenges_ES
dc.publisherEMBO Press
dc.relation.projectFISinfo:eu-repo/grantAgreement/ES/SAF2014-60442-JINes_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/ES/RTI2018-093330-B/FEDER-EUes_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/ES/SAF2013-45111-Res_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/ES/SAF2013-44866-Res_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/ES/RTI2018-095582-B-I00es_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/ES/RED2018-102723-Tes_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/ES/SAF2017-92729-EXPes_ES
dc.relation.publisherversionhttps://doi.org/10.15252/embj.2019104324es_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Telómeros y Telomerasaes_ES
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subject.meshCell Differentiationes_ES
dc.subject.meshDNA Methylationes_ES
dc.subject.meshEpigenesis, Genetices_ES
dc.subject.meshAnimalses_ES
dc.subject.meshCell Linees_ES
dc.subject.meshDNA (Cytosine-5-)-Methyltransferaseses_ES
dc.subject.meshDNA Methyltransferase 3Aes_ES
dc.subject.meshHumanses_ES
dc.subject.meshInduced Pluripotent Stem Cellses_ES
dc.subject.meshMicees_ES
dc.subject.meshMicroRNAses_ES
dc.subject.meshDNA Methyltransferase 3Bes_ES
dc.titleTransient exposure to miR-203 enhances the differentiation capacity of established pluripotent stem cells.es_ES
dc.typejournal articlees_ES
dc.type.hasVersionVoRes_ES
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