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Curr Biol. 2011 Jan 11;21(1):45-52. doi: 10.1016/j.cub.2010.11.049. Epub 2010 Dec 17.

A high proliferation rate is required for cell reprogramming and maintenance of human embryonic stem cell identity.

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Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.


Human embryonic stem (hES) cells show an atypical cell-cycle regulation characterized by a high proliferation rate and a short G1 phase. In fact, a shortened G1 phase might protect ES cells from external signals inducing differentiation, as shown for certain stem cells. It has been suggested that self-renewal and pluripotency are intimately linked to cell-cycle regulation in ES cells, although little is known about the overall importance of the cell-cycle machinery in maintaining ES cell identity. An appealing model to address whether the acquisition of stem cell properties is linked to cell-cycle regulation emerged with the ability to generate induced pluripotent stem (iPS) cells by expression of defined transcription factors. Here, we show that the characteristic cell-cycle signature of hES cells is acquired as an early event in cell reprogramming. We demonstrate that induction of cell proliferation increases reprogramming efficiency, whereas cell-cycle arrest inhibits successful reprogramming. Furthermore, we show that cell-cycle arrest is sufficient to drive hES cells toward irreversible differentiation. Our results establish a link that intertwines the mechanisms of cell-cycle control with the mechanisms underlying the acquisition and maintenance of ES cell identity.

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