Increasing Notch signaling antagonizes PRC2-mediated silencing to promote reprograming of germ cells into neurons

  1. Stefanie Seelk
  2. Irene Adrian-Kalchhauser
  3. Balázs Hargitai
  4. Martina Hajduskova
  5. Silvia Gutnik
  6. Baris Tursun  Is a corresponding author
  7. Rafal Ciosk  Is a corresponding author
  1. Max-Delbrück-Center for Molecular Medicine, Germany
  2. Friedrich Miescher Institute for Biomedical Research, Switzerland

Abstract

Cell-fate reprograming is at the heart of development, yet very little is known about the molecular mechanisms promoting or inhibiting reprograming in intact organisms. In the C. elegans germline, reprograming germ cells into somatic cells requires chromatin perturbation. Here, we describe that such reprograming is facilitated by GLP-1/Notch signaling pathway. This is surprising, since this pathway is best known for maintaining undifferentiated germline stem cells/progenitors. Through a combination of genetics, tissue-specific transcriptome analysis, and functional studies of candidate genes, we uncovered a possible explanation for this unexpected role of GLP-1/Notch. We propose that GLP-1/Notch promotes reprograming by activating specific genes, silenced by the Polycomb repressive complex 2 (PRC2), and identify the conserved histone demethylase UTX-1 as a crucial GLP-1/Notch target facilitating reprograming. These findings have wide implications, ranging from development to diseases associated with abnormal Notch signaling.

Article and author information

Author details

  1. Stefanie Seelk

    Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Irene Adrian-Kalchhauser

    Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Balázs Hargitai

    Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  4. Martina Hajduskova

    Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Silvia Gutnik

    Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  6. Baris Tursun

    Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine, Berlin, Germany
    For correspondence
    baris.tursun@mdc-berlin.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7293-8629
  7. Rafal Ciosk

    Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
    For correspondence
    rafal.ciosk@fmi.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2234-6216

Funding

European Research Council (ERC-2014-STG #637530 - REPROWORM)

  • Baris Tursun

Helmholtz-Gemeinschaft (MDC PhD)

  • Stefanie Seelk

European Research Council (FP7-PEOPLE-2012-CIG #333922- REPROL53U48)

  • Baris Tursun

European Cooperation in Science and Technology (SBFI C15.0038)

  • Rafal Ciosk

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Julie Ahringer, University of Cambridge, United Kingdom

Version history

  1. Received: February 23, 2016
  2. Accepted: September 6, 2016
  3. Accepted Manuscript published: September 7, 2016 (version 1)
  4. Accepted Manuscript updated: September 8, 2016 (version 2)
  5. Version of Record published: September 30, 2016 (version 3)

Copyright

© 2016, Seelk et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Stefanie Seelk
  2. Irene Adrian-Kalchhauser
  3. Balázs Hargitai
  4. Martina Hajduskova
  5. Silvia Gutnik
  6. Baris Tursun
  7. Rafal Ciosk
(2016)
Increasing Notch signaling antagonizes PRC2-mediated silencing to promote reprograming of germ cells into neurons
eLife 5:e15477.
https://doi.org/10.7554/eLife.15477

Share this article

https://doi.org/10.7554/eLife.15477

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