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Elife. 2019 Sep 25;8. pii: e48561. doi: 10.7554/eLife.48561.

Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells.

Author information

1
The Francis Crick Institute, London, United Kingdom.
2
Institut du Cerveau et de la Moelle Epinière, ICM, Inserm U 1127, CNRS UMR 7225, Sorbonne Université, Paris, France.
3
Department of Cell Biology, Erasmus MC, Rotterdam, Netherlands.
4
Institute of Molecular Biotechnology (IMBA), Vienna Biocenter Campus (VBC), Vienna, Austria.

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 (NSCs) 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 NSCs 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 NSC cultures. Id4 sequesters Ascl1 heterodimerization partner E47, promoting Ascl1 protein degradation and stem cell quiescence. Our results highlight the importance of non-transcriptional mechanisms for the maintenance of NSC 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.

KEYWORDS:

ID proteins; adult neurogenesis; adult stem cell; hippocampus; mouse; neuroscience; quiescence; regenerative medicine; stem cells

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