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Zinc Maintains Embryonic Stem Cell Pluripotency and Multilineage Differentiation Potential via AKT Activation

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Zinc Maintains Embryonic Stem Cell Pluripotency and Multilineage Differentiation Potential via AKT Activation

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dc.contributor.author Mnatsakanyan, Hayk es_ES
dc.contributor.author Sabater i Serra, Roser es_ES
dc.contributor.author Salmerón Sánchez, Manuel es_ES
dc.contributor.author Rico Tortosa, Patricia María es_ES
dc.date.accessioned 2020-12-12T04:32:21Z
dc.date.available 2020-12-12T04:32:21Z
dc.date.issued 2019-08-30 es_ES
dc.identifier.uri http://hdl.handle.net/10251/156945
dc.description.abstract [EN] Embryonic stem cells (ESCs) possess remarkable abilities, as they can differentiate into all cell types (pluripotency) and be self-renewing, giving rise to two identical cells. These characteristics make ESCs a powerful research tool in fundamental embryogenesis as well as candidates for use in regenerative medicine. Significant efforts have been devoted to developing protocols to control ESC fate, including soluble and complex cocktails of growth factors and small molecules seeking to activate/inhibit key signaling pathways for the maintenance of pluripotency states or activate differentiation. Here we describe a novel method for the effective maintenance of mouse ESCs, avoiding the supplementation of complex inhibitory cocktails or cytokines, e.g., LIF. We show that the addition of zinc to ESC cultures leads to a stable pluripotent state that shares biochemical, transcriptional and karyotypic features with the classical LIF treatment. We demonstrate for the first time that ESCs maintained in long-term cultures with added zinc, are capable of sustaining a stable ESCs pluripotent phenotype, as well as differentiating efficiently upon external stimulation. We show that zinc promotes long-term ESC self-renewal (>30 days) via activation of ZIP7 and AKT signaling pathways. Furthermore, the combination of zinc with LIF results in a synergistic effect that enhances LIF effects, increases AKT and STAT3 activity, promotes the expression of pluripotency regulators and avoids the expression of differentiation markers. es_ES
dc.description.sponsorship PR acknowledges support from the Spanish Ministry of Science, Innovation and Universities (RTI2018-096794), and Fondo Europeo de Desarrollo Regional (FEDER). CIBER-BBN was an initiative funded by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund. MS-S acknowledges support from the UK Engineering and Physical Sciences Research Council (EPSRC - EP/P001114/1). es_ES
dc.language Inglés es_ES
dc.publisher Frontiers Media SA es_ES
dc.relation.ispartof Frontiers in Cell and Developmental Biology es_ES
dc.rights Reconocimiento (by) es_ES
dc.subject Zinc es_ES
dc.subject ZIP7 es_ES
dc.subject Stemness maintenance es_ES
dc.subject Embryonic stem cells (ESC) es_ES
dc.subject AKT es_ES
dc.subject.classification INGENIERIA ELECTRICA es_ES
dc.subject.classification MAQUINAS Y MOTORES TERMICOS es_ES
dc.subject.classification FISICA APLICADA es_ES
dc.title Zinc Maintains Embryonic Stem Cell Pluripotency and Multilineage Differentiation Potential via AKT Activation es_ES
dc.type Artículo es_ES
dc.identifier.doi 10.3389/fcell.2019.00180 es_ES
dc.relation.projectID info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/RTI2018-096794-B-I00/ES/DISEÑO DE MICROENTORNOS CELULARES PARA PROMOVER LA MECANOTRANSDUCCION SINERGICA DE CANALES DE IONES E INTEGRINAS/ es_ES
dc.relation.projectID info:eu-repo/grantAgreement/UKRI//EP%2FP001114%2F1/GB/Engineering growth factor microenvironments - a new therapeutic paradigm for regenerative medicine/ es_ES
dc.rights.accessRights Abierto es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Física Aplicada - Departament de Física Aplicada es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Termodinámica Aplicada - Departament de Termodinàmica Aplicada es_ES
dc.contributor.affiliation Universitat Politècnica de València. Departamento de Ingeniería Eléctrica - Departament d'Enginyeria Elèctrica es_ES
dc.contributor.affiliation Universitat Politècnica de València. Centro de Biomateriales e Ingeniería Tisular - Centre de Biomaterials i Enginyeria Tissular es_ES
dc.description.bibliographicCitation Mnatsakanyan, H.; Sabater I Serra, R.; Salmerón Sánchez, M.; Rico Tortosa, PM. (2019). Zinc Maintains Embryonic Stem Cell Pluripotency and Multilineage Differentiation Potential via AKT Activation. Frontiers in Cell and Developmental Biology. 7:1-17. https://doi.org/10.3389/fcell.2019.00180 es_ES
dc.description.accrualMethod S es_ES
dc.relation.publisherversion https://doi.org/10.3389/fcell.2019.00180 es_ES
dc.description.upvformatpinicio 1 es_ES
dc.description.upvformatpfin 17 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion es_ES
dc.description.volume 7 es_ES
dc.identifier.eissn 2296-634X es_ES
dc.identifier.pmid 31544103 es_ES
dc.identifier.pmcid PMC6728745 es_ES
dc.relation.pasarela S\398306 es_ES
dc.contributor.funder Instituto de Salud Carlos III es_ES
dc.contributor.funder UK Research and Innovation es_ES
dc.contributor.funder European Regional Development Fund es_ES
dc.contributor.funder Ministerio de Ciencia e Innovación es_ES
dc.contributor.funder Engineering and Physical Sciences Research Council, Reino Unido es_ES
dc.contributor.funder Agencia Estatal de Investigación es_ES
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