IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v448y2007i7151d10.1038_nature05934.html
   My bibliography  Save this article

Generation of germline-competent induced pluripotent stem cells

Author

Listed:
  • Keisuke Okita

    (Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan)

  • Tomoko Ichisaka

    (Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
    CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan)

  • Shinya Yamanaka

    (Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
    CREST, Japan Science and Technology Agency, Kawaguchi 332-0012, Japan)

Abstract

We have previously shown that pluripotent stem cells can be induced from mouse fibroblasts by retroviral introduction of Oct3/4 (also called Pou5f1), Sox2, c-Myc and Klf4, and subsequent selection for Fbx15 (also called Fbxo15) expression. These induced pluripotent stem (iPS) cells (hereafter called Fbx15 iPS cells) are similar to embryonic stem (ES) cells in morphology, proliferation and teratoma formation; however, they are different with regards to gene expression and DNA methylation patterns, and fail to produce adult chimaeras. Here we show that selection for Nanog expression results in germline-competent iPS cells with increased ES-cell-like gene expression and DNA methylation patterns compared with Fbx15 iPS cells. The four transgenes (Oct3/4, Sox2, c-myc and Klf4) were strongly silenced in Nanog iPS cells. We obtained adult chimaeras from seven Nanog iPS cell clones, with one clone being transmitted through the germ line to the next generation. Approximately 20% of the offspring developed tumours attributable to reactivation of the c-myc transgene. Thus, iPS cells competent for germline chimaeras can be obtained from fibroblasts, but retroviral introduction of c-Myc should be avoided for clinical application.

Suggested Citation

  • Keisuke Okita & Tomoko Ichisaka & Shinya Yamanaka, 2007. "Generation of germline-competent induced pluripotent stem cells," Nature, Nature, vol. 448(7151), pages 313-317, July.
    • Handle: RePEc:nat:nature:v:448:y:2007:i:7151:d:10.1038_nature05934
    DOI: 10.1038/nature05934
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature05934
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature05934?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Ryoko Araki & Tomo Suga & Yuko Hoki & Kaori Imadome & Misato Sunayama & Satoshi Kamimura & Mayumi Fujita & Masumi Abe, 2024. "iPS cell generation-associated point mutations include many C > T substitutions via different cytosine modification mechanisms," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Barbara Graham & Jacqueline Stevens & Phatia Wells & Jennifer Sims & Christian Rogers & Sophia S. Leggett & Stephen Ekunwe & Kenneth Ndebele, 2014. "Enhancement of Arsenic Trioxide-Mediated Changes in Human Induced Pluripotent Stem Cells (IPS)," IJERPH, MDPI, vol. 11(7), pages 1-13, July.
    3. Xiang Meng & Ruixuan Jia & Xinping Zhao & Fan Zhang & Shaohong Chen & Shicheng Yu & Xiaozhen Liu & Hongliang Dou & Xuefeng Feng & Jinlu Zhang & Ni Wang & Boling Xu & Liping Yang, 2024. "In vivo genome editing via CRISPR/Cas9-mediated homology-independent targeted integration for Bietti crystalline corneoretinal dystrophy treatment," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:448:y:2007:i:7151:d:10.1038_nature05934. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.