IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v6y2015i1d10.1038_ncomms7188.html
   My bibliography  Save this article

Collaborative rewiring of the pluripotency network by chromatin and signalling modulating pathways

Author

Listed:
  • Khoa A. Tran

    (Wisconsin Institute for Discovery, University of Wisconsin
    Molecular and Cellular Pharmacology Program, University of Wisconsin)

  • Steven A. Jackson

    (Wisconsin Institute for Discovery, University of Wisconsin)

  • Zachariah P.G. Olufs

    (Wisconsin Institute for Discovery, University of Wisconsin)

  • Nur Zafirah Zaidan

    (Wisconsin Institute for Discovery, University of Wisconsin)

  • Ning Leng

    (University of Wisconsin)

  • Christina Kendziorski

    (University of Wisconsin)

  • Sushmita Roy

    (Wisconsin Institute for Discovery, University of Wisconsin
    University of Wisconsin)

  • Rupa Sridharan

    (Wisconsin Institute for Discovery, University of Wisconsin
    University of Wisconsin)

Abstract

Reprogramming of somatic cells to induced pluripotent stem cells (iPSCs) represents a profound change in cell fate. Here, we show that combining ascorbic acid (AA) and 2i (MAP kinase and GSK inhibitors) increases the efficiency of reprogramming from fibroblasts and synergistically enhances conversion of partially reprogrammed intermediates to the iPSC state. AA and 2i induce differential transcriptional responses, each leading to the activation of specific pluripotency loci. A unique cohort of pluripotency genes including Esrrb require both stimuli for activation. Temporally, AA-dependent histone demethylase effects are important early, whereas Tet enzyme effects are required throughout the conversion. 2i function could partially be replaced by depletion of components of the epidermal growth factor (EGF) and insulin growth factor pathways, indicating that they act as barriers to reprogramming. Accordingly, reduction in the levels of the EGF receptor gene contributes to the activation of Esrrb. These results provide insight into the rewiring of the pluripotency network at the late stage of reprogramming.

Suggested Citation

  • Khoa A. Tran & Steven A. Jackson & Zachariah P.G. Olufs & Nur Zafirah Zaidan & Ning Leng & Christina Kendziorski & Sushmita Roy & Rupa Sridharan, 2015. "Collaborative rewiring of the pluripotency network by chromatin and signalling modulating pathways," Nature Communications, Nature, vol. 6(1), pages 1-14, May.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7188
    DOI: 10.1038/ncomms7188
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms7188
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/ncomms7188?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
    ---><---

    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:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7188. 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.