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Stem cells

The great iPS barrier

Nature Reviews Molecular Cell Biology volume 10, pages 578–579 (2009)Cite this article

The INK4/ARF locus encodes p15INK4B (also known as CDKN2B), p16INK4A (also known as CDKN2A) and ARF, which positively regulate the p53 and retinoblastoma tumour suppressor pathways to inhibit cell proliferation and promote cellular senescence. p21 (also known as CDKN1A), which is upregulated by p53, also inhibits proliferation and promotes senescence. Data from the five new studies suggest that depletion of p53, ARF, p16INK4A or p21 can increase the kinetics and efficiency of iPS cell generation.

Hong et al. showed that the absence of, or a reduction in, p53 increases the efficiency of iPS cell generation from mouse and human fibroblasts. In fact, all of these studies, using various approaches, showed that p53 depletion enhances iPS cell generation. Kawamura et al. also enhanced the reprogramming of mouse embryonic fibroblasts (MEFs) by reducing the level of p21 or ARF. As ARF inhibits p53 degradation, ARF knockdown might enhance reprogramming by decreasing p53 stability.

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ORIGINAL RESEARCH PAPERS

  1. Hong, H. et al. Suppression of induced pluripotent stem cell generation by the p53–p21 pathway. Nature 9 Aug 2009 (doi:10.1038/nature08235)

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  2. Kawamura, T. et al. Linking the p53 tumor suppressor pathway to somatic cell reprogramming. Nature 9 Aug 2009 (doi:10.1038/nature08311)

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  3. Li, H. et al. The Ink4/Arf locus is a barrier for iPS reprogramming. Nature 9 Aug 2009 (doi:10.1038/nature08290)

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  5. Utikal, J. et al. Immortalization eliminates a roadblock during cellular reprogramming into iPS cells. Nature 9 Aug 2009 (doi:10.1038/nature08285)

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Authors
  1. Katharine H. Wrighton
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Wrighton, K. The great iPS barrier. Nat Rev Mol Cell Biol 10, 578–579 (2009). https://doi.org/10.1038/nrm2753

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