IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v7y2016i1d10.1038_ncomms11247.html
   My bibliography  Save this article

A programmable synthetic lineage-control network that differentiates human IPSCs into glucose-sensitive insulin-secreting beta-like cells

Author

Listed:
  • Pratik Saxena

    (ETH Zurich)

  • Boon Chin Heng

    (ETH Zurich
    Present address: Department of Endodontics, Faculty of Dentistry, The University of Hong Kong, Pokfulam, Hong Kong)

  • Peng Bai

    (ETH Zurich)

  • Marc Folcher

    (ETH Zurich)

  • Henryk Zulewski

    (ETH Zurich
    Diabetes and Metabolism, University Hospital Basel
    Present address: Division of Endocrinology and Diabetes, Stadtspital Triemli, Birmensdorferstrasse 497, CH-8063 Zurich, Switzerland)

  • Martin Fussenegger

    (ETH Zurich
    Faculty of Science, University of Basel)

Abstract

Synthetic biology has advanced the design of standardized transcription control devices that programme cellular behaviour. By coupling synthetic signalling cascade- and transcription factor-based gene switches with reverse and differential sensitivity to the licensed food additive vanillic acid, we designed a synthetic lineage-control network combining vanillic acid-triggered mutually exclusive expression switches for the transcription factors Ngn3 (neurogenin 3; OFF-ON-OFF) and Pdx1 (pancreatic and duodenal homeobox 1; ON-OFF-ON) with the concomitant induction of MafA (V-maf musculoaponeurotic fibrosarcoma oncogene homologue A; OFF-ON). This designer network consisting of different network topologies orchestrating the timely control of transgenic and genomic Ngn3, Pdx1 and MafA variants is able to programme human induced pluripotent stem cells (hIPSCs)-derived pancreatic progenitor cells into glucose-sensitive insulin-secreting beta-like cells, whose glucose-stimulated insulin-release dynamics are comparable to human pancreatic islets. Synthetic lineage-control networks may provide the missing link to genetically programme somatic cells into autologous cell phenotypes for regenerative medicine.

Suggested Citation

  • Pratik Saxena & Boon Chin Heng & Peng Bai & Marc Folcher & Henryk Zulewski & Martin Fussenegger, 2016. "A programmable synthetic lineage-control network that differentiates human IPSCs into glucose-sensitive insulin-secreting beta-like cells," Nature Communications, Nature, vol. 7(1), pages 1-14, September.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11247
    DOI: 10.1038/ncomms11247
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms11247
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms11247?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
    ---><---

    Citations

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


    Cited by:

    1. Adam M. Zahm & William S. Owens & Samuel R. Himes & Braden S. Fallon & Kathleen E. Rondem & Alexa N. Gormick & Joshua S. Bloom & Sriram Kosuri & Henry Chan & Justin G. English, 2024. "A massively parallel reporter assay library to screen short synthetic promoters in mammalian cells," Nature Communications, Nature, vol. 15(1), pages 1-14, 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:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11247. 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.