Sox5 controls the establishment of quiescence in neural stem cells during postnatal development.

Adult stem cell niches relays in the acquisition of a reversible state of quiescence to ensure long-lasting DNA integrity and cell expansion. Neural stem cells (NSCs) in the dentate gyrus (DG) enter quiescence before the adult hippocampal neurogenic niche is fully established. However, the mechanism...

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Main Authors: Cristina Medina-Menéndez, Paula Tirado-Melendro, Lingling Li, Pilar Rodríguez-Martín, Elena Melgarejo-de la Peña, Mario Díaz-García, María Valdés-Bescós, Rafael López-Sansegundo, Aixa V Morales
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-07-01
Series:PLoS Biology
Online Access:https://doi.org/10.1371/journal.pbio.3002654
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author Cristina Medina-Menéndez
Paula Tirado-Melendro
Lingling Li
Pilar Rodríguez-Martín
Elena Melgarejo-de la Peña
Mario Díaz-García
María Valdés-Bescós
Rafael López-Sansegundo
Aixa V Morales
author_facet Cristina Medina-Menéndez
Paula Tirado-Melendro
Lingling Li
Pilar Rodríguez-Martín
Elena Melgarejo-de la Peña
Mario Díaz-García
María Valdés-Bescós
Rafael López-Sansegundo
Aixa V Morales
author_sort Cristina Medina-Menéndez
collection DOAJ
description Adult stem cell niches relays in the acquisition of a reversible state of quiescence to ensure long-lasting DNA integrity and cell expansion. Neural stem cells (NSCs) in the dentate gyrus (DG) enter quiescence before the adult hippocampal neurogenic niche is fully established. However, the mechanisms controlling NSC first quiescence entry and quiescence deepness are largely unknown. Using conditional mutant mouse during embryonic or postnatal stages, we have determined that transcription factor Sox5 is required to restrict first entry in quiescence. Moreover, we have found a critical window during the second postnatal week when NSCs build up a shallow quiescent state. Loss of Sox5 leads to an excess of NSCs in shallow quiescence, which are prone to activate, leading to a neurogenic burst in the adult DG and precocious depletion of the NSC pool. Mechanistically, Sox5 prevents an excess of BMP canonical signaling, a pathway that is required to maintain the correct levels of NSC quiescence during the second postnatal week. In conclusion, our results demonstrate that Sox5 is required to control the correct balance between shallow and deep quiescence during the first postnatal weeks of DG development, a balance which is essential for establishing long-lasting adult neurogenesis.
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institution Kabale University
issn 1544-9173
1545-7885
language English
publishDate 2025-07-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS Biology
spelling doaj-art-829be9e76adb438cbe956ec00a06d1242025-08-20T03:40:46ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852025-07-01237e300265410.1371/journal.pbio.3002654Sox5 controls the establishment of quiescence in neural stem cells during postnatal development.Cristina Medina-MenéndezPaula Tirado-MelendroLingling LiPilar Rodríguez-MartínElena Melgarejo-de la PeñaMario Díaz-GarcíaMaría Valdés-BescósRafael López-SansegundoAixa V MoralesAdult stem cell niches relays in the acquisition of a reversible state of quiescence to ensure long-lasting DNA integrity and cell expansion. Neural stem cells (NSCs) in the dentate gyrus (DG) enter quiescence before the adult hippocampal neurogenic niche is fully established. However, the mechanisms controlling NSC first quiescence entry and quiescence deepness are largely unknown. Using conditional mutant mouse during embryonic or postnatal stages, we have determined that transcription factor Sox5 is required to restrict first entry in quiescence. Moreover, we have found a critical window during the second postnatal week when NSCs build up a shallow quiescent state. Loss of Sox5 leads to an excess of NSCs in shallow quiescence, which are prone to activate, leading to a neurogenic burst in the adult DG and precocious depletion of the NSC pool. Mechanistically, Sox5 prevents an excess of BMP canonical signaling, a pathway that is required to maintain the correct levels of NSC quiescence during the second postnatal week. In conclusion, our results demonstrate that Sox5 is required to control the correct balance between shallow and deep quiescence during the first postnatal weeks of DG development, a balance which is essential for establishing long-lasting adult neurogenesis.https://doi.org/10.1371/journal.pbio.3002654
spellingShingle Cristina Medina-Menéndez
Paula Tirado-Melendro
Lingling Li
Pilar Rodríguez-Martín
Elena Melgarejo-de la Peña
Mario Díaz-García
María Valdés-Bescós
Rafael López-Sansegundo
Aixa V Morales
Sox5 controls the establishment of quiescence in neural stem cells during postnatal development.
PLoS Biology
title Sox5 controls the establishment of quiescence in neural stem cells during postnatal development.
title_full Sox5 controls the establishment of quiescence in neural stem cells during postnatal development.
title_fullStr Sox5 controls the establishment of quiescence in neural stem cells during postnatal development.
title_full_unstemmed Sox5 controls the establishment of quiescence in neural stem cells during postnatal development.
title_short Sox5 controls the establishment of quiescence in neural stem cells during postnatal development.
title_sort sox5 controls the establishment of quiescence in neural stem cells during postnatal development
url https://doi.org/10.1371/journal.pbio.3002654
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