• Open Access

Concise Review: The Dynamics of Induced Pluripotency and Its Behavior Captured in Gene Network Motifs§

Authors

  • Mauro J. Muraro,

    1. Swammerdam Institute for Life Sciences, Netherlands Institute for Systems Biology, University of Amsterdam, Amsterdam, The Netherlands
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  • Hermannus Kempe,

    1. Swammerdam Institute for Life Sciences, Netherlands Institute for Systems Biology, University of Amsterdam, Amsterdam, The Netherlands
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  • Pernette J. Verschure

    Corresponding author
    1. Swammerdam Institute for Life Sciences, Netherlands Institute for Systems Biology, University of Amsterdam, Amsterdam, The Netherlands
    • Swammerdam Institute for Life Sciences, Netherlands Institute for Systems Biology, University of Amsterdam, Science Park 904, 1098 XH Amsterdam, The Netherlands
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    • Telephone: 31-205255151; Fax: 31-205257934


  • Author contributions: M.J.M. and H.K.: collection and/or assembly of data, data analysis and interpretation, and manuscript writing; P.J.V.: conception and design, financial support, data analysis and interpretation, manuscript writing, and final approval of manuscript.

  • Disclosure of potential conflicts of interest is found at the end of this article.

  • §

    First published online in STEM CELLSEXPRESS January 29, 2013.

Abstract

The flexibility of cellular identity is clearly demonstrated by the possibility to reprogram fully differentiated somatic cells to induced pluripotent stem (iPS) cells through forced expression of a set of transcription factors. The generation of iPS cells is of great interest as they provide a tremendous potential for regenerative medicine and an attractive platform to investigate pluripotency. Despite having gathered much attention, the molecular details and responsible gene regulatory networks during the reprogramming process are largely unresolved. In this review, we analyze the sequence and dynamics of reprogramming to construct a timeline of the molecular events taking place during induced pluripotency. We use this timeline as a road map to explore the distinct phases of the reprogramming process and to suggest gene network motifs that are able to describe its systems behavior. We conclude that the gene networks involved in reprogramming comprise several feedforward loops combined with autoregulatory behavior and one or more AND gate motifs that can explain the observed dynamics of induced pluripotency. Our proposed timeline and derived gene network motif behavior could serve as a tool to understand the systems behavior of reprogramming and identify key transitions and/or transcription factors that influence somatic cell reprogramming. Such a systems biology strategy could provide ways to define and explore the use of additional regulatory factors acting at defined gene network motifs to potentially overcome the current challenges of inefficient, slow, and partial somatic cell reprogramming and hence set ground of using iPS cells for clinical and therapeutic use. STEM CELLS 2013;31:838–848

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