Identificador persistente para citar o vincular este elemento: http://hdl.handle.net/10553/52438
Título: Regulated fluctuations in Nanog expression mediate cell fate decisions in embryonic stem cells
Autores/as: Kalmar, Tibor
Lim, Chea
Hayward, Penelope
Muñoz-Descalzo, Silvia 
Nichols, Jennifer
Garcia-Ojalvo, Jordi
Martinez Arias, Alfonso
Clasificación UNESCO: 32 Ciencias médicas
320102 Genética clínica
Palabras clave: Pluripotency
Cell differentiation
Gene expression
Genetic networks
Population dynamics, et al.
Fecha de publicación: 2009
Publicación seriada: PLoS Biology 
Resumen: 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.
URI: http://hdl.handle.net/10553/52438
ISSN: 1544-9173
DOI: 10.1371/journal.pbio.1000149
Fuente: PLoS Biology[ISSN 1544-9173],v. 7 (7) (e1000149) (Julio 2009)
Colección:Artículos
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