1. Neuroscience
  2. Stem Cells and Regenerative Medicine
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Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells

  1. Isabelle Maria Blomfield
  2. Brenda Rocamonde
  3. Maria del Mar Masdeu
  4. Eskeatnaf Mulugeta
  5. Stefania Vaga
  6. Debbie LC van den Berg
  7. Emmanuelle Huillard
  8. Francois Guillemot  Is a corresponding author
  9. Noelia Urbán  Is a corresponding author
  1. The Francis Crick Institute, United Kingdom
  2. Institut du Cerveau et de la Moelle Epinière (ICM), France
  3. Erasmus MC, Netherlands
Research Article
  • Cited 23
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Cite this article as: eLife 2019;8:e48561 doi: 10.7554/eLife.48561

Abstract

Quiescence is essential for the long-term maintenance of adult stem cells but how stem cells maintain quiescence is poorly understood. Here we show that neural stem cells in the adult mouse hippocampus actively transcribe the pro-activation factor Ascl1 regardless of their activated or quiescent states. We found that the inhibitor of DNA binding protein Id4 is enriched in quiescent neural stem cells and that elimination of Id4 results in abnormal accumulation of Ascl1 protein and premature stem cell activation. Accordingly, Id4 and other Id proteins promote elimination of Ascl1 protein in neural stem cell cultures. Id4 sequesters Ascl1 heterodimerisation partner E47, promoting Ascl1 protein degradation and stem cell quiescence. Our results highlight the importance of non-transcriptional mechanisms for the maintenance of neural stem cell quiescence and reveal a role for Id4 as a quiescence-inducing factor, in contrast with its role of promoting the proliferation of embryonic neural progenitors.

Data availability

Sequencing data have been deposited in GEO under accession code GSE116997

The following data sets were generated

Article and author information

Author details

  1. Isabelle Maria Blomfield

    The Francis Crick Institute, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4412-0226
  2. Brenda Rocamonde

    Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France
    Competing interests
    No competing interests declared.
  3. Maria del Mar Masdeu

    The Francis Crick Institute, London, United Kingdom
    Competing interests
    No competing interests declared.
  4. Eskeatnaf Mulugeta

    Department of Cell Biology, Erasmus MC, Rotterdam, Netherlands
    Competing interests
    No competing interests declared.
  5. Stefania Vaga

    The Francis Crick Institute, London, United Kingdom
    Competing interests
    No competing interests declared.
  6. Debbie LC van den Berg

    Department of Cell Biology, Erasmus MC, Rotterdam, Netherlands
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6026-8808
  7. Emmanuelle Huillard

    Institut du Cerveau et de la Moelle Epinière (ICM), Paris, France
    Competing interests
    No competing interests declared.
  8. Francois Guillemot

    The Francis Crick Institute, London, United Kingdom
    For correspondence
    Francois.Guillemot@crick.ac.uk
    Competing interests
    Francois Guillemot, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0432-5067
  9. Noelia Urbán

    The Francis Crick Institute, London, United Kingdom
    For correspondence
    noelia.urban@imba.oeaw.ac.at
    Competing interests
    No competing interests declared.

Funding

Francis Crick Institute (FC0010089)

  • Eskeatnaf Mulugeta

Medical Research Council (U117570528)

  • Francois Guillemot

Wellcome (106187/Z/14/Z)

  • Francois Guillemot

H2020 Marie Skłodowska-Curie Actions (799214)

  • Debbie LC van den Berg

Ligue Contre le Cancer (PJA 20131200481)

  • Emmanuelle Huillard

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

Ethics

Animal experimentation: All procedures involving animals and their care were performed in accordance with the guidelines of the Francis Crick Institute, national guidelines and laws. This study was approved by the Animal Ethics Committee and by the UK Home Office (PPL PB04755CC). All surgery was performed under terminal pentobarbital anaesthesia, and every effort was made to minimise suffering.

Reviewing Editor

  1. Gary L Westbrook, Oregon Health and Science University, United States

Publication history

  1. Received: May 17, 2019
  2. Accepted: September 24, 2019
  3. Accepted Manuscript published: September 25, 2019 (version 1)
  4. Version of Record published: October 22, 2019 (version 2)

Copyright

© 2019, Blomfield 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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