β-Catenin Fluctuates in Mouse ESCs and Is Essential for Nanog-Mediated Reprogramming of Somatic Cells to Pluripotency

The Wnt/β-catenin pathway and Nanog are key regulators of embryonic stem cell (ESC) pluripotency and the reprogramming of somatic cells. Here, we demonstrate that the repression of Dkk1 by Nanog, which leads indirectly to β-catenin activation, is essential for reprogramming after fusion of ESCs over...

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Main Authors: Lucia Marucci, Elisa Pedone, Umberto Di Vicino, Blanca Sanuy-Escribano, Mark Isalan, Maria Pia Cosma
Format: Article
Language:English
Published: Elsevier 2014-09-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124714006743
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author Lucia Marucci
Elisa Pedone
Umberto Di Vicino
Blanca Sanuy-Escribano
Mark Isalan
Maria Pia Cosma
author_facet Lucia Marucci
Elisa Pedone
Umberto Di Vicino
Blanca Sanuy-Escribano
Mark Isalan
Maria Pia Cosma
author_sort Lucia Marucci
collection DOAJ
description The Wnt/β-catenin pathway and Nanog are key regulators of embryonic stem cell (ESC) pluripotency and the reprogramming of somatic cells. Here, we demonstrate that the repression of Dkk1 by Nanog, which leads indirectly to β-catenin activation, is essential for reprogramming after fusion of ESCs overexpressing Nanog. In addition, β-catenin is necessary in Nanog-dependent conversion of preinduced pluripotent stem cells (pre-iPSCs) into iPSCs. The activation of β-catenin by Nanog causes fluctuations of β-catenin in ESCs cultured in serum plus leukemia inhibitory factor (serum+LIF) medium, in which protein levels of key pluripotency factors are heterogeneous. In 2i+LIF medium, which favors propagation of ESCs in a ground state of pluripotency with many pluripotency genes losing mosaic expression, we show Nanog-independent β-catenin fluctuations. Overall, we demonstrate Nanog and β-catenin cooperation in establishing naive pluripotency during the reprogramming process and their correlated heterogeneity in ESCs primed toward differentiation.
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spelling doaj.art-62d9551f9305477e9f402b32f52abcf32022-12-21T18:02:21ZengElsevierCell Reports2211-12472014-09-01861686169610.1016/j.celrep.2014.08.011β-Catenin Fluctuates in Mouse ESCs and Is Essential for Nanog-Mediated Reprogramming of Somatic Cells to PluripotencyLucia Marucci0Elisa Pedone1Umberto Di Vicino2Blanca Sanuy-Escribano3Mark Isalan4Maria Pia Cosma5Centre for Genomic Regulation (CRG), 08003 Barcelona, SpainCentre for Genomic Regulation (CRG), 08003 Barcelona, SpainCentre for Genomic Regulation (CRG), 08003 Barcelona, SpainCentre for Genomic Regulation (CRG), 08003 Barcelona, SpainCentre for Genomic Regulation (CRG), 08003 Barcelona, SpainCentre for Genomic Regulation (CRG), 08003 Barcelona, SpainThe Wnt/β-catenin pathway and Nanog are key regulators of embryonic stem cell (ESC) pluripotency and the reprogramming of somatic cells. Here, we demonstrate that the repression of Dkk1 by Nanog, which leads indirectly to β-catenin activation, is essential for reprogramming after fusion of ESCs overexpressing Nanog. In addition, β-catenin is necessary in Nanog-dependent conversion of preinduced pluripotent stem cells (pre-iPSCs) into iPSCs. The activation of β-catenin by Nanog causes fluctuations of β-catenin in ESCs cultured in serum plus leukemia inhibitory factor (serum+LIF) medium, in which protein levels of key pluripotency factors are heterogeneous. In 2i+LIF medium, which favors propagation of ESCs in a ground state of pluripotency with many pluripotency genes losing mosaic expression, we show Nanog-independent β-catenin fluctuations. Overall, we demonstrate Nanog and β-catenin cooperation in establishing naive pluripotency during the reprogramming process and their correlated heterogeneity in ESCs primed toward differentiation.http://www.sciencedirect.com/science/article/pii/S2211124714006743
spellingShingle Lucia Marucci
Elisa Pedone
Umberto Di Vicino
Blanca Sanuy-Escribano
Mark Isalan
Maria Pia Cosma
β-Catenin Fluctuates in Mouse ESCs and Is Essential for Nanog-Mediated Reprogramming of Somatic Cells to Pluripotency
Cell Reports
title β-Catenin Fluctuates in Mouse ESCs and Is Essential for Nanog-Mediated Reprogramming of Somatic Cells to Pluripotency
title_full β-Catenin Fluctuates in Mouse ESCs and Is Essential for Nanog-Mediated Reprogramming of Somatic Cells to Pluripotency
title_fullStr β-Catenin Fluctuates in Mouse ESCs and Is Essential for Nanog-Mediated Reprogramming of Somatic Cells to Pluripotency
title_full_unstemmed β-Catenin Fluctuates in Mouse ESCs and Is Essential for Nanog-Mediated Reprogramming of Somatic Cells to Pluripotency
title_short β-Catenin Fluctuates in Mouse ESCs and Is Essential for Nanog-Mediated Reprogramming of Somatic Cells to Pluripotency
title_sort β catenin fluctuates in mouse escs and is essential for nanog mediated reprogramming of somatic cells to pluripotency
url http://www.sciencedirect.com/science/article/pii/S2211124714006743
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