Direct cell reprogramming is a stochastic process amenable to acceleration View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-12

AUTHORS

Jacob Hanna, Krishanu Saha, Bernardo Pando, Jeroen van Zon, Christopher J. Lengner, Menno P. Creyghton, Alexander van Oudenaarden, Rudolf Jaenisch

ABSTRACT

Direct reprogramming of somatic cells into induced pluripotent stem (iPS) cells can be achieved by overexpression of Oct4, Sox2, Klf4 and c-Myc transcription factors, but only a minority of donor somatic cells can be reprogrammed to pluripotency. Here we demonstrate that reprogramming by these transcription factors is a continuous stochastic process where almost all mouse donor cells eventually give rise to iPS cells on continued growth and transcription factor expression. Additional inhibition of the p53/p21 pathway or overexpression of Lin28 increased the cell division rate and resulted in an accelerated kinetics of iPS cell formation that was directly proportional to the increase in cell proliferation. In contrast, Nanog overexpression accelerated reprogramming in a predominantly cell-division-rate-independent manner. Quantitative analyses define distinct cell-division-rate-dependent and -independent modes for accelerating the stochastic course of reprogramming, and suggest that the number of cell divisions is a key parameter driving epigenetic reprogramming to pluripotency. More... »

PAGES

595

References to SciGraph publications

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  • Journal

    TITLE

    Nature

    ISSUE

    7273

    VOLUME

    462

    Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nature08592

    DOI

    http://dx.doi.org/10.1038/nature08592

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1030291386

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/19898493


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