Cellular heterogeneity is now considered an inherent property of most stem cell types, including pluripotent stem cells, somatic\nstem cells, and cancer stem cells, and this heterogeneity can exist at the epigenetic, transcriptional, and posttranscriptional levels.\nSeveral studies have indicated that the stochastic activation of signaling networks may promote heterogeneity and further that this\nheterogeneity may be reduced by their inhibition. But why different cells in the same culture respond in a nonuniform manner to\nthe identical exogenous signals has remained unclear. Recent studies nowdemonstrate that the cell cycle position directly influences\nlineage specification and specifically that pluripotent stem cells initiate their differentiation fromtheG1 phase. These studies suggest\nthat cells in G1 are uniquely ââ?¬Å?poisedââ?¬Â to undergo cell specification. G1 cells are therefore more prone to respond to differentiation\ncues, which may explain the heterogeneity of developmental factors, such as Gata6, and pluripotency factors, such as Nanog, in\nstem cell cultures. Overall, this raises the possibility that G1 serves as a ââ?¬Å?Differentiation Induction Point.ââ?¬Â In this review, we will\nreexamine the literature describing heterogeneity of pluripotent stem cells, while highlighting the role of the cell cycle as a major\ndeterminant
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