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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Format: | Article |
Language: | English |
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Elsevier
2014-09-01
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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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issn | 2211-1247 |
language | English |
last_indexed | 2024-12-23T03:04:21Z |
publishDate | 2014-09-01 |
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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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