IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v454y2008i7200d10.1038_nature07056.html
   My bibliography  Save this article

Dissecting direct reprogramming through integrative genomic analysis

Author

Listed:
  • Tarjei S. Mikkelsen

    (Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Division of Health Sciences and Technology,)

  • Jacob Hanna

    (Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Xiaolan Zhang

    (Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Manching Ku

    (Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA)

  • Marius Wernig

    (Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Patrick Schorderet

    (Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Bradley E. Bernstein

    (Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA
    Harvard Medical School, Boston, Massachusetts 02115, USA)

  • Rudolf Jaenisch

    (Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA)

  • Eric S. Lander

    (Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Harvard Medical School, Boston, Massachusetts 02114, USA)

  • Alexander Meissner

    (Broad Institute of MIT and Harvard, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA
    Harvard University, Cambridge, Massachusetts 02138, USA)

Abstract

Somatic cells can be reprogrammed to a pluripotent state through the ectopic expression of defined transcription factors. Understanding the mechanism and kinetics of this transformation may shed light on the nature of developmental potency and suggest strategies with improved efficiency or safety. Here we report an integrative genomic analysis of reprogramming of mouse fibroblasts and B lymphocytes. Lineage-committed cells show a complex response to the ectopic expression involving induction of genes downstream of individual reprogramming factors. Fully reprogrammed cells show gene expression and epigenetic states that are highly similar to embryonic stem cells. In contrast, stable partially reprogrammed cell lines show reactivation of a distinctive subset of stem-cell-related genes, incomplete repression of lineage-specifying transcription factors, and DNA hypermethylation at pluripotency-related loci. These observations suggest that some cells may become trapped in partially reprogrammed states owing to incomplete repression of transcription factors, and that DNA de-methylation is an inefficient step in the transition to pluripotency. We demonstrate that RNA inhibition of transcription factors can facilitate reprogramming, and that treatment with DNA methyltransferase inhibitors can improve the overall efficiency of the reprogramming process.

Suggested Citation

  • Tarjei S. Mikkelsen & Jacob Hanna & Xiaolan Zhang & Manching Ku & Marius Wernig & Patrick Schorderet & Bradley E. Bernstein & Rudolf Jaenisch & Eric S. Lander & Alexander Meissner, 2008. "Dissecting direct reprogramming through integrative genomic analysis," Nature, Nature, vol. 454(7200), pages 49-55, July.
    • Handle: RePEc:nat:nature:v:454:y:2008:i:7200:d:10.1038_nature07056
    DOI: 10.1038/nature07056
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature07056
    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/nature07056?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. Bo Wang & Chen Li & Jin Ming & Linlin Wu & Shicai Fang & Yi Huang & Lihui Lin & He Liu & Junqi Kuang & Chengchen Zhao & Xingnan Huang & Huijian Feng & Jing Guo & Xuejie Yang & Liman Guo & Xiaofei Zhan, 2023. "The NuRD complex cooperates with SALL4 to orchestrate reprogramming," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. María José Pino-Barrio & Elisa García-García & Pablo Menéndez & Alberto Martínez-Serrano, 2015. "V-Myc Immortalizes Human Neural Stem Cells in the Absence of Pluripotency-Associated Traits," PLOS ONE, Public Library of Science, vol. 10(3), pages 1-13, March.
    3. Marianne Lønnebotn & Natalia El-Merhie & John W. Holloway & William Horsnell & Susanne Krauss-Etschmann & Francisco Gómez Real & Cecilie Svanes, 2018. "Environmental Impact on Health across Generations: Policy Meets Biology. A Review of Animal and Human Models," Challenges, MDPI, vol. 9(2), pages 1-16, 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:454:y:2008:i:7200:d:10.1038_nature07056. 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.