Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells
- The Francis Crick Institute, United Kingdom
- Institut du Cerveau et de la Moelle Epinière (ICM), France
- Erasmus MC, Netherlands
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
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Id4 maintains quiescence of adult hippocampal stem cellsNCBI Gene Expression Omnibus, GSE116997.
Article and author information
Author details
Isabelle Maria Blomfield
Debbie LC van den Berg
Francois Guillemot
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.
Reviewing Editor
- Gary L Westbrook, Oregon Health and Science University, United States
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.
Version history
- Received: May 17, 2019
- Accepted: September 24, 2019
- Accepted Manuscript published: September 25, 2019 (version 1)
- 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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Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells
eLife 8:e48561.
https://doi.org/10.7554/eLife.48561
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