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Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells
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 quies...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805120/ https://www.ncbi.nlm.nih.gov/pubmed/31552825 http://dx.doi.org/10.7554/eLife.48561 |
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author | Blomfield, Isabelle Maria Rocamonde, Brenda Masdeu, Maria del Mar Mulugeta, Eskeatnaf Vaga, Stefania van den Berg, Debbie LC Huillard, Emmanuelle Guillemot, François Urbán, Noelia |
author_facet | Blomfield, Isabelle Maria Rocamonde, Brenda Masdeu, Maria del Mar Mulugeta, Eskeatnaf Vaga, Stefania van den Berg, Debbie LC Huillard, Emmanuelle Guillemot, François Urbán, Noelia |
author_sort | Blomfield, Isabelle Maria |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6805120 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-68051202019-10-24 Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells Blomfield, Isabelle Maria Rocamonde, Brenda Masdeu, Maria del Mar Mulugeta, Eskeatnaf Vaga, Stefania van den Berg, Debbie LC Huillard, Emmanuelle Guillemot, François Urbán, Noelia eLife Neuroscience 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. eLife Sciences Publications, Ltd 2019-09-25 /pmc/articles/PMC6805120/ /pubmed/31552825 http://dx.doi.org/10.7554/eLife.48561 Text en © 2019, Blomfield et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Blomfield, Isabelle Maria Rocamonde, Brenda Masdeu, Maria del Mar Mulugeta, Eskeatnaf Vaga, Stefania van den Berg, Debbie LC Huillard, Emmanuelle Guillemot, François Urbán, Noelia Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells |
title | Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells |
title_full | Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells |
title_fullStr | Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells |
title_full_unstemmed | Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells |
title_short | Id4 promotes the elimination of the pro-activation factor Ascl1 to maintain quiescence of adult hippocampal stem cells |
title_sort | id4 promotes the elimination of the pro-activation factor ascl1 to maintain quiescence of adult hippocampal stem cells |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805120/ https://www.ncbi.nlm.nih.gov/pubmed/31552825 http://dx.doi.org/10.7554/eLife.48561 |
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