Zinc Maintains Embryonic Stem Cell Pluripotency and Multilineage Differentiation Potential via AKT Activation
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 rege...
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Frontiers Media S.A.
2019-08-01
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Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2019.00180/full |
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author | Hayk Mnatsakanyan Roser Sabater i Serra Roser Sabater i Serra Manuel Salmeron-Sanchez Manuel Salmeron-Sanchez Manuel Salmeron-Sanchez Patricia Rico Patricia Rico |
author_facet | Hayk Mnatsakanyan Roser Sabater i Serra Roser Sabater i Serra Manuel Salmeron-Sanchez Manuel Salmeron-Sanchez Manuel Salmeron-Sanchez Patricia Rico Patricia Rico |
author_sort | Hayk Mnatsakanyan |
collection | DOAJ |
description | 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. |
first_indexed | 2024-04-13T22:15:30Z |
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id | doaj.art-5a2a50e0c72e4d599a234ddc3a95a293 |
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issn | 2296-634X |
language | English |
last_indexed | 2024-04-13T22:15:30Z |
publishDate | 2019-08-01 |
publisher | Frontiers Media S.A. |
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series | Frontiers in Cell and Developmental Biology |
spelling | doaj.art-5a2a50e0c72e4d599a234ddc3a95a2932022-12-22T02:27:32ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2019-08-01710.3389/fcell.2019.00180479764Zinc Maintains Embryonic Stem Cell Pluripotency and Multilineage Differentiation Potential via AKT ActivationHayk Mnatsakanyan0Roser Sabater i Serra1Roser Sabater i Serra2Manuel Salmeron-Sanchez3Manuel Salmeron-Sanchez4Manuel Salmeron-Sanchez5Patricia Rico6Patricia Rico7Centre for Biomaterials and Tissue Engineering (CBIT), Universitat Politècnica de València, Valencia, SpainCentre for Biomaterials and Tissue Engineering (CBIT), Universitat Politècnica de València, Valencia, SpainBiomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, SpainCentre for Biomaterials and Tissue Engineering (CBIT), Universitat Politècnica de València, Valencia, SpainBiomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, SpainDivision of Biomedical Engineering, Centre for the Cellular Microenvironment, School of Engineering, University of Glasgow, Glasgow, United KingdomCentre for Biomaterials and Tissue Engineering (CBIT), Universitat Politècnica de València, Valencia, SpainBiomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Madrid, SpainEmbryonic 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.https://www.frontiersin.org/article/10.3389/fcell.2019.00180/fullzincZIP7stemness maintenanceembryonic stem cells (ESC)AKT |
spellingShingle | Hayk Mnatsakanyan Roser Sabater i Serra Roser Sabater i Serra Manuel Salmeron-Sanchez Manuel Salmeron-Sanchez Manuel Salmeron-Sanchez Patricia Rico Patricia Rico Zinc Maintains Embryonic Stem Cell Pluripotency and Multilineage Differentiation Potential via AKT Activation Frontiers in Cell and Developmental Biology zinc ZIP7 stemness maintenance embryonic stem cells (ESC) AKT |
title | Zinc Maintains Embryonic Stem Cell Pluripotency and Multilineage Differentiation Potential via AKT Activation |
title_full | Zinc Maintains Embryonic Stem Cell Pluripotency and Multilineage Differentiation Potential via AKT Activation |
title_fullStr | Zinc Maintains Embryonic Stem Cell Pluripotency and Multilineage Differentiation Potential via AKT Activation |
title_full_unstemmed | Zinc Maintains Embryonic Stem Cell Pluripotency and Multilineage Differentiation Potential via AKT Activation |
title_short | Zinc Maintains Embryonic Stem Cell Pluripotency and Multilineage Differentiation Potential via AKT Activation |
title_sort | zinc maintains embryonic stem cell pluripotency and multilineage differentiation potential via akt activation |
topic | zinc ZIP7 stemness maintenance embryonic stem cells (ESC) AKT |
url | https://www.frontiersin.org/article/10.3389/fcell.2019.00180/full |
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