Direct cell reprogramming is a stochastic process amenable to acceleration
Name
Jaenisch Direct_Cell.pdf
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Author(s)
Jaenisch, Rudolf
Lengner, Christopher J.
van Oudenaarden, Alexander
Van Zon, Jeroen Sebastiaan
Pando, Bernardo Fabian
Saha, Krishanu
Hanna, Jacob
Creyghton, Menno P.
Date Issued
December 2009
Journal
Nature
Publisher
Nature Publishing Group
Citation
Hanna, Jacob et al. “Direct cell reprogramming is a stochastic process amenable to acceleration.” Nature 462.7273 (2009): 595-601. © 2009 Nature Publishing Group.
Version
Author's final manuscript
Abstract
Direct reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) 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 is a continuous stochastic process where almost all donor cells eventually give rise to iPSCs upon continued growth and transcription factor expression. Additional inhibition the p53/p21 pathway or overexpression of Lin28 increased the cell division rate and resulted in an accelerated kinetics of iPSC 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.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Physics
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/nature08592
