Regulated fluctuations in nanog expression mediate cell fate decisions in embryonic stem cells.

There is evidence that pluripotency of mouse embryonic stem (ES) cells is associated with the activity of a network of transcription factors with Sox2, Oct4, and Nanog at the core. Using fluorescent reporters for the expression of Nanog, we observed that a population of ES cells is best described by...

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Autores principales:	Tibor Kalmar, Chea Lim, Penelope Hayward, Silvia Muñoz-Descalzo, Jennifer Nichols, Jordi Garcia-Ojalvo, Alfonso Martinez Arias
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/e807a2692875499cb27725e43dbaf267
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spelling	oai:doaj.org-article:e807a2692875499cb27725e43dbaf2672021-11-25T05:34:06ZRegulated fluctuations in nanog expression mediate cell fate decisions in embryonic stem cells.1544-91731545-788510.1371/journal.pbio.1000149https://doaj.org/article/e807a2692875499cb27725e43dbaf2672009-07-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19582141/pdf/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885There is evidence that pluripotency of mouse embryonic stem (ES) cells is associated with the activity of a network of transcription factors with Sox2, Oct4, and Nanog at the core. Using fluorescent reporters for the expression of Nanog, we observed that a population of ES cells is best described by a dynamic distribution of Nanog expression characterized by two peaks defined by high (HN) and low (LN) Nanog expression. Typically, the LN state is 5%-20% of the total population, depending on the culture conditions. Modelling of the activity of Nanog reveals that a simple network of Oct4/Sox2 and Nanog activity can account for the observed distribution and its properties as long as the transcriptional activity is tuned by transcriptional noise. The model also predicts that the LN state is unstable, something that is born out experimentally. While in this state, cells can differentiate. We suggest that transcriptional fluctuations in Nanog expression are an essential element of the pluripotent state and that the function of Sox2, Oct4, and Nanog is to act as a network that promotes and maintains transcriptional noise to interfere with the differentiation signals.Tibor KalmarChea LimPenelope HaywardSilvia Muñoz-DescalzoJennifer NicholsJordi Garcia-OjalvoAlfonso Martinez AriasPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 7, Iss 7, p e1000149 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Tibor Kalmar Chea Lim Penelope Hayward Silvia Muñoz-Descalzo Jennifer Nichols Jordi Garcia-Ojalvo Alfonso Martinez Arias Regulated fluctuations in nanog expression mediate cell fate decisions in embryonic stem cells.
description	There is evidence that pluripotency of mouse embryonic stem (ES) cells is associated with the activity of a network of transcription factors with Sox2, Oct4, and Nanog at the core. Using fluorescent reporters for the expression of Nanog, we observed that a population of ES cells is best described by a dynamic distribution of Nanog expression characterized by two peaks defined by high (HN) and low (LN) Nanog expression. Typically, the LN state is 5%-20% of the total population, depending on the culture conditions. Modelling of the activity of Nanog reveals that a simple network of Oct4/Sox2 and Nanog activity can account for the observed distribution and its properties as long as the transcriptional activity is tuned by transcriptional noise. The model also predicts that the LN state is unstable, something that is born out experimentally. While in this state, cells can differentiate. We suggest that transcriptional fluctuations in Nanog expression are an essential element of the pluripotent state and that the function of Sox2, Oct4, and Nanog is to act as a network that promotes and maintains transcriptional noise to interfere with the differentiation signals.
format	article
author	Tibor Kalmar Chea Lim Penelope Hayward Silvia Muñoz-Descalzo Jennifer Nichols Jordi Garcia-Ojalvo Alfonso Martinez Arias
author_facet	Tibor Kalmar Chea Lim Penelope Hayward Silvia Muñoz-Descalzo Jennifer Nichols Jordi Garcia-Ojalvo Alfonso Martinez Arias
author_sort	Tibor Kalmar
title	Regulated fluctuations in nanog expression mediate cell fate decisions in embryonic stem cells.
title_short	Regulated fluctuations in nanog expression mediate cell fate decisions in embryonic stem cells.
title_full	Regulated fluctuations in nanog expression mediate cell fate decisions in embryonic stem cells.
title_fullStr	Regulated fluctuations in nanog expression mediate cell fate decisions in embryonic stem cells.
title_full_unstemmed	Regulated fluctuations in nanog expression mediate cell fate decisions in embryonic stem cells.
title_sort	regulated fluctuations in nanog expression mediate cell fate decisions in embryonic stem cells.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/e807a2692875499cb27725e43dbaf267
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Regulated fluctuations in nanog expression mediate cell fate decisions in embryonic stem cells.

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