Human embryonic stem cells are pre-mitotically committed to self-renewal and acquire a lengthened G1 phase upon lineage programming

Authors

  • Klaus A. Becker,

    1. Department of Cell Biology, Cancer Center and Center for Stem Cell Biology and Regenerative Medicine, University of Massachusetts Medical School, Worcester, Massachusetts
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  • Janet L. Stein,

    1. Department of Cell Biology, Cancer Center and Center for Stem Cell Biology and Regenerative Medicine, University of Massachusetts Medical School, Worcester, Massachusetts
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  • Jane B. Lian,

    1. Department of Cell Biology, Cancer Center and Center for Stem Cell Biology and Regenerative Medicine, University of Massachusetts Medical School, Worcester, Massachusetts
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  • Andre J. van Wijnen,

    1. Department of Cell Biology, Cancer Center and Center for Stem Cell Biology and Regenerative Medicine, University of Massachusetts Medical School, Worcester, Massachusetts
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  • Gary S. Stein

    Corresponding author
    1. Department of Cell Biology, Cancer Center and Center for Stem Cell Biology and Regenerative Medicine, University of Massachusetts Medical School, Worcester, Massachusetts
    • Department of Cell Biology and Cancer Center, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655.
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  • The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

Abstract

Self-renewal of human embryonic stem (hES) cells proceeds by a unique abbreviated cell cycle with a shortened G1 phase and distinctions in molecular cell cycle regulatory parameters. In this study, we show that early lineage-commitment of pluripotent hES cells modifies cell cycle kinetics. Human ES cells acquire a lengthened G1 within 72 h after lineage-programming is initiated, as reflected by loss of the pluripotency factor Oct4 and alterations in nuclear morphology. In hES cells that maintain the pristine pluripotent state, we find that autocrine mechanisms contribute to sustaining the abbreviated cell cycle. Our data show that naïve and mitotically synchronized pluripotent hES cells are competent to initiate two consecutive S phases in the absence of external growth factors. We conclude that short-term self-renewal of pluripotent hES cells occurs autonomously, in part due to secreted factors, and that pluripotency is functionally linked to the abbreviated hES cell cycle. J. Cell. Physiol. 222:103–110, 2010. © 2009 Wiley-Liss, Inc.

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