DNA Hypermethylation in Somatic Cells Correlates with Higher Reprogramming Efficiency§

Authors

  • María J. Barrero,

    1. Center for Regenerative Medicine in Barcelona, Barcelona, Catalonia, Spain
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  • María Berdasco,

    1. Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain
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  • Ida Paramonov,

    1. Center for Regenerative Medicine in Barcelona, Barcelona, Catalonia, Spain
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  • Josipa Bilic,

    1. Center for Regenerative Medicine in Barcelona, Barcelona, Catalonia, Spain
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  • Marianna Vitaloni,

    1. Center for Regenerative Medicine in Barcelona, Barcelona, Catalonia, Spain
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  • Manel Esteller,

    Corresponding author
    1. Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Catalonia, Spain
    2. Institució Catalana de Recerca I Estudis Avançats (ICREA), Barcelona, Catalonia, Spain
    • Cancer Epigenetics Group, Cancer Epigenetics and Biology Program (PEBC), Bellvitge Institute for Biomedical Research (IDIBELL), L'Hospitalet de Llobregat, 08908 Barcelona, Catalonia, Spain
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    • Telephone: +34-93-2607253; Fax: +34-93-2607219

  • Juan Carlos Izpisua Belmonte

    Corresponding author
    1. Center for Regenerative Medicine in Barcelona, Barcelona, Catalonia, Spain
    2. Salk Institute for Biological Studies, La Jolla, California, USA
    • Salk Institute for Biological Studies, 10010 N. Torrey Pines Rd., La Jolla, CA 92037 USA
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  • Author contributions: M.J.B. and M.B.: conceived and designed the project, provided materials, collected and interpreted data, provided financial support, and wrote manuscript; I.P.: performed data analysis and interpretation, J.B. and M.V.: provided materials and collected data; M.E. and J.C.I.B.: conceived, designed and supervised the project, provided financial support, wrote manuscript, and final approval of manuscript. M.J.B and M.B. contributed equally to this article.

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

  • §

    First published online in STEM CELLSEXPRESS May 31, 2012.

Abstract

The efficiency of somatic cell reprogramming to pluripotency using defined factors is dramatically affected by the cell type of origin. Here, we show that human keratinocytes, which can be reprogrammed at a higher efficiency than fibroblast [Nat Biotechnol 2008;26:1276-1284], share more genes hypermethylated at CpGs with human embryonic stem cells (ESCs) than other somatic cells frequently used for reprogramming. Moreover, pluripotent cells reprogrammed from keratinocytes (KiPS) are more similar to ESCs than those reprogrammed from fibroblasts (FiPS) in regard to DNA methylation levels, mostly due to the presence of genes that fail to acquire high levels of DNA methylation in FiPS cells. We propose that higher reprogramming efficiency correlates with the hypermethylation of tissue-specific genes rather than with a more permissive pluripotency gene network. STEM CELLS2012;30:1696–1702

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