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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...

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Autores principales: Blomfield, Isabelle Maria, Rocamonde, Brenda, Masdeu, Maria del Mar, Mulugeta, Eskeatnaf, Vaga, Stefania, van den Berg, Debbie LC, Huillard, Emmanuelle, Guillemot, François, Urbán, Noelia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
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.
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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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