Cell Cycle-Driven Heterogeneity: On the Road to Demystifying the Transitions between “Poised” and “Restricted” Pluripotent Cell States

Cellular heterogeneity is now considered an inherent property of most stem cell types, including pluripotent stem cells, somatic stem cells, and cancer stem cells, and this heterogeneity can exist at the epigenetic, transcriptional, and posttranscriptional levels. Several studies have indicated that...

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Main Author: Amar M. Singh
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:Stem Cells International
Online Access:http://dx.doi.org/10.1155/2015/219514
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author Amar M. Singh
author_facet Amar M. Singh
author_sort Amar M. Singh
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description Cellular heterogeneity is now considered an inherent property of most stem cell types, including pluripotent stem cells, somatic stem cells, and cancer stem cells, and this heterogeneity can exist at the epigenetic, transcriptional, and posttranscriptional levels. Several studies have indicated that the stochastic activation of signaling networks may promote heterogeneity and further that this heterogeneity may be reduced by their inhibition. But why different cells in the same culture respond in a nonuniform manner to the identical exogenous signals has remained unclear. Recent studies now demonstrate that the cell cycle position directly influences lineage specification and specifically that pluripotent stem cells initiate their differentiation from the G1 phase. These studies suggest that cells in G1 are uniquely “poised” to undergo cell specification. G1 cells are therefore more prone to respond to differentiation cues, which may explain the heterogeneity of developmental factors, such as Gata6, and pluripotency factors, such as Nanog, in stem cell cultures. Overall, this raises the possibility that G1 serves as a “Differentiation Induction Point.” In this review, we will reexamine the literature describing heterogeneity of pluripotent stem cells, while highlighting the role of the cell cycle as a major determinant.
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spelling doaj-art-6e2c9d3a4d4b43659eb8f01a2b1818872025-08-20T02:06:31ZengWileyStem Cells International1687-966X1687-96782015-01-01201510.1155/2015/219514219514Cell Cycle-Driven Heterogeneity: On the Road to Demystifying the Transitions between “Poised” and “Restricted” Pluripotent Cell StatesAmar M. Singh0Department of Biochemistry and Molecular Biology, Paul D. Coverdell Center for Biomedical and Health Sciences, The University of Georgia, 500 D.W. Brooks Drive, Athens, GA 30602, USACellular heterogeneity is now considered an inherent property of most stem cell types, including pluripotent stem cells, somatic stem cells, and cancer stem cells, and this heterogeneity can exist at the epigenetic, transcriptional, and posttranscriptional levels. Several studies have indicated that the stochastic activation of signaling networks may promote heterogeneity and further that this heterogeneity may be reduced by their inhibition. But why different cells in the same culture respond in a nonuniform manner to the identical exogenous signals has remained unclear. Recent studies now demonstrate that the cell cycle position directly influences lineage specification and specifically that pluripotent stem cells initiate their differentiation from the G1 phase. These studies suggest that cells in G1 are uniquely “poised” to undergo cell specification. G1 cells are therefore more prone to respond to differentiation cues, which may explain the heterogeneity of developmental factors, such as Gata6, and pluripotency factors, such as Nanog, in stem cell cultures. Overall, this raises the possibility that G1 serves as a “Differentiation Induction Point.” In this review, we will reexamine the literature describing heterogeneity of pluripotent stem cells, while highlighting the role of the cell cycle as a major determinant.http://dx.doi.org/10.1155/2015/219514
spellingShingle Amar M. Singh
Cell Cycle-Driven Heterogeneity: On the Road to Demystifying the Transitions between “Poised” and “Restricted” Pluripotent Cell States
Stem Cells International
title Cell Cycle-Driven Heterogeneity: On the Road to Demystifying the Transitions between “Poised” and “Restricted” Pluripotent Cell States
title_full Cell Cycle-Driven Heterogeneity: On the Road to Demystifying the Transitions between “Poised” and “Restricted” Pluripotent Cell States
title_fullStr Cell Cycle-Driven Heterogeneity: On the Road to Demystifying the Transitions between “Poised” and “Restricted” Pluripotent Cell States
title_full_unstemmed Cell Cycle-Driven Heterogeneity: On the Road to Demystifying the Transitions between “Poised” and “Restricted” Pluripotent Cell States
title_short Cell Cycle-Driven Heterogeneity: On the Road to Demystifying the Transitions between “Poised” and “Restricted” Pluripotent Cell States
title_sort cell cycle driven heterogeneity on the road to demystifying the transitions between poised and restricted pluripotent cell states
url http://dx.doi.org/10.1155/2015/219514
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