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Nanog Variability and Pluripotency Regulation of Embryonic Stem Cells - Insights from a Mathematical Model Analysis

The expression of the transcription factors Oct4, Sox2, and Nanog is commonly associated with pluripotency of mouse embryonic stem (ES) cells. However, recent observations suggest that ES cell populations are heterogeneous with respect to the expression of Nanog and that individual ES cells reversib...

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Detalles Bibliográficos
Autores principales: Glauche, Ingmar, Herberg, Maria, Roeder, Ingo
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2888652/
https://www.ncbi.nlm.nih.gov/pubmed/20574542
http://dx.doi.org/10.1371/journal.pone.0011238
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author Glauche, Ingmar
Herberg, Maria
Roeder, Ingo
author_facet Glauche, Ingmar
Herberg, Maria
Roeder, Ingo
author_sort Glauche, Ingmar
collection PubMed
description The expression of the transcription factors Oct4, Sox2, and Nanog is commonly associated with pluripotency of mouse embryonic stem (ES) cells. However, recent observations suggest that ES cell populations are heterogeneous with respect to the expression of Nanog and that individual ES cells reversibly change their Nanog expression level. Furthermore, it has been shown that cells exhibiting a low Nanog level are more likely to undergo differentiation. Applying a novel mathematical transcription factor network model we explore mechanisms and feedback regulations to describe the observed variation of the Nanog levels in mouse ES cells. In particular we show that these variations can occur under different assumptions yielding similar experimental characteristics. Based on model predictions we propose experimental strategies to distinguish between these explanations. Concluding from our results we argue that the heterogeneity with respect to the Nanog concentrations is most likely a functional element to control the differentiation propensity of an ES cell population. Furthermore, we provide a conceptual framework that consistently explains Nanog variability and a potential “gate-keeper” function of Nanog expression with respect to the control of ES cell differentiation.
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spelling pubmed-28886522010-06-23 Nanog Variability and Pluripotency Regulation of Embryonic Stem Cells - Insights from a Mathematical Model Analysis Glauche, Ingmar Herberg, Maria Roeder, Ingo PLoS One Research Article The expression of the transcription factors Oct4, Sox2, and Nanog is commonly associated with pluripotency of mouse embryonic stem (ES) cells. However, recent observations suggest that ES cell populations are heterogeneous with respect to the expression of Nanog and that individual ES cells reversibly change their Nanog expression level. Furthermore, it has been shown that cells exhibiting a low Nanog level are more likely to undergo differentiation. Applying a novel mathematical transcription factor network model we explore mechanisms and feedback regulations to describe the observed variation of the Nanog levels in mouse ES cells. In particular we show that these variations can occur under different assumptions yielding similar experimental characteristics. Based on model predictions we propose experimental strategies to distinguish between these explanations. Concluding from our results we argue that the heterogeneity with respect to the Nanog concentrations is most likely a functional element to control the differentiation propensity of an ES cell population. Furthermore, we provide a conceptual framework that consistently explains Nanog variability and a potential “gate-keeper” function of Nanog expression with respect to the control of ES cell differentiation. Public Library of Science 2010-06-21 /pmc/articles/PMC2888652/ /pubmed/20574542 http://dx.doi.org/10.1371/journal.pone.0011238 Text en Glauche et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Glauche, Ingmar
Herberg, Maria
Roeder, Ingo
Nanog Variability and Pluripotency Regulation of Embryonic Stem Cells - Insights from a Mathematical Model Analysis
title Nanog Variability and Pluripotency Regulation of Embryonic Stem Cells - Insights from a Mathematical Model Analysis
title_full Nanog Variability and Pluripotency Regulation of Embryonic Stem Cells - Insights from a Mathematical Model Analysis
title_fullStr Nanog Variability and Pluripotency Regulation of Embryonic Stem Cells - Insights from a Mathematical Model Analysis
title_full_unstemmed Nanog Variability and Pluripotency Regulation of Embryonic Stem Cells - Insights from a Mathematical Model Analysis
title_short Nanog Variability and Pluripotency Regulation of Embryonic Stem Cells - Insights from a Mathematical Model Analysis
title_sort nanog variability and pluripotency regulation of embryonic stem cells - insights from a mathematical model analysis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2888652/
https://www.ncbi.nlm.nih.gov/pubmed/20574542
http://dx.doi.org/10.1371/journal.pone.0011238
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