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Immortalization eliminates a roadblock during cellular reprogramming into iPS cells

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  • Jochen Utikal

    (Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Harvard Stem Cell Institute, 185 Cambridge Street, Boston, Massachusetts 02114, USA
    Harvard University, Cambridge, Massachusetts 02138, USA
    Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl-University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68135 Mannheim, Germany)

  • Jose M. Polo

    (Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Harvard Stem Cell Institute, 185 Cambridge Street, Boston, Massachusetts 02114, USA
    Harvard University, Cambridge, Massachusetts 02138, USA)

  • Matthias Stadtfeld

    (Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Harvard Stem Cell Institute, 185 Cambridge Street, Boston, Massachusetts 02114, USA
    Harvard University, Cambridge, Massachusetts 02138, USA)

  • Nimet Maherali

    (Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Harvard Stem Cell Institute, 185 Cambridge Street, Boston, Massachusetts 02114, USA
    Harvard University, Cambridge, Massachusetts 02138, USA
    Harvard University, 7 Divinity Avenue, Cambridge, Massachusetts 02138, USA)

  • Warakorn Kulalert

    (Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Harvard Stem Cell Institute, 185 Cambridge Street, Boston, Massachusetts 02114, USA
    Harvard University, Cambridge, Massachusetts 02138, USA)

  • Ryan M. Walsh

    (Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Harvard Stem Cell Institute, 185 Cambridge Street, Boston, Massachusetts 02114, USA
    Harvard University, Cambridge, Massachusetts 02138, USA)

  • Adam Khalil

    (Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Harvard Stem Cell Institute, 185 Cambridge Street, Boston, Massachusetts 02114, USA
    Harvard University, Cambridge, Massachusetts 02138, USA)

  • James G. Rheinwald

    (Brigham and Women’s Hospital and Harvard Skin Disease Research Center, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA)

  • Konrad Hochedlinger

    (Massachusetts General Hospital Cancer Center and Center for Regenerative Medicine, Harvard Stem Cell Institute, 185 Cambridge Street, Boston, Massachusetts 02114, USA
    Harvard University, Cambridge, Massachusetts 02138, USA)

Abstract

On iPS cells and p53: removing the roadblock Pluripotency can be induced in somatic cells by overexpression of a set of transcription factors. The process has extremely low efficiency and slow kinetics. Here Utikal et al. show that cells with low endogenous p19Arf levels and immortal fibroblasts deficient for components of the Ink4a/Arf/p53 pathway yield iPS colonies with a threefold faster kinetics and at a significantly higher efficiency compared with wild-type cells, reaching frequencies of up to 100%. Genetic deletion of p53 in cellular subpopulations that normally fail to reprogram rescues their ability to produce iPS cells.

Suggested Citation

  • Jochen Utikal & Jose M. Polo & Matthias Stadtfeld & Nimet Maherali & Warakorn Kulalert & Ryan M. Walsh & Adam Khalil & James G. Rheinwald & Konrad Hochedlinger, 2009. "Immortalization eliminates a roadblock during cellular reprogramming into iPS cells," Nature, Nature, vol. 460(7259), pages 1145-1148, August.
    • Handle: RePEc:nat:nature:v:460:y:2009:i:7259:d:10.1038_nature08285
    DOI: 10.1038/nature08285
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    Cited by:

    1. Siti Razila Abdul Razak & Kazuko Ueno & Naoya Takayama & Naoki Nariai & Masao Nagasaki & Rika Saito & Hideto Koso & Chen-Yi Lai & Miyako Murakami & Koichiro Tsuji & Tatsuo Michiue & Hiromitsu Nakauchi, 2013. "Profiling of MicroRNA in Human and Mouse ES and iPS Cells Reveals Overlapping but Distinct MicroRNA Expression Patterns," PLOS ONE, Public Library of Science, vol. 8(9), pages 1-16, September.
    2. Patricia Gerdes & Sue Mei Lim & Adam D. Ewing & Michael R. Larcombe & Dorothy Chan & Francisco J. Sanchez-Luque & Lucinda Walker & Alexander L. Carleton & Cini James & Anja S. Knaupp & Patricia E. Car, 2022. "Retrotransposon instability dominates the acquired mutation landscape of mouse induced pluripotent stem cells," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Tomoe Ueyama & Shu Nakao & Tasuku Tsukamoto & Dai Ihara & Yukihiro Harada & Yuka Akagi & Sae Nakagawa & Teruhisa Kawamura & Takahiro Sogo & Yasuyuki S Kida, 2018. "PTEN/Akt Axis is Involved in Somatic Cell Reprogramming to Mouse iPS Cells," Biomedical Journal of Scientific & Technical Research, Biomedical Research Network+, LLC, vol. 11(5), pages 8789-8795, December.

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