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Enhanced lysosomal degradation maintains the quiescent state of neural stem cells

Quiescence is important for sustaining neural stem cells (NSCs) in the adult brain over the lifespan. Lysosomes are digestive organelles that degrade membrane receptors after they undergo endolysosomal membrane trafficking. Enlarged lysosomes are present in quiescent NSCs (qNSCs) in the subventricul...

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Autores principales: Kobayashi, Taeko, Piao, Wenhui, Takamura, Toshiya, Kori, Hiroshi, Miyachi, Hitoshi, Kitano, Satsuki, Iwamoto, Yumiko, Yamada, Mayumi, Imayoshi, Itaru, Shioda, Seiji, Ballabio, Andrea, Kageyama, Ryoichiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884460/
https://www.ncbi.nlm.nih.gov/pubmed/31784517
http://dx.doi.org/10.1038/s41467-019-13203-4
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author Kobayashi, Taeko
Piao, Wenhui
Takamura, Toshiya
Kori, Hiroshi
Miyachi, Hitoshi
Kitano, Satsuki
Iwamoto, Yumiko
Yamada, Mayumi
Imayoshi, Itaru
Shioda, Seiji
Ballabio, Andrea
Kageyama, Ryoichiro
author_facet Kobayashi, Taeko
Piao, Wenhui
Takamura, Toshiya
Kori, Hiroshi
Miyachi, Hitoshi
Kitano, Satsuki
Iwamoto, Yumiko
Yamada, Mayumi
Imayoshi, Itaru
Shioda, Seiji
Ballabio, Andrea
Kageyama, Ryoichiro
author_sort Kobayashi, Taeko
collection PubMed
description Quiescence is important for sustaining neural stem cells (NSCs) in the adult brain over the lifespan. Lysosomes are digestive organelles that degrade membrane receptors after they undergo endolysosomal membrane trafficking. Enlarged lysosomes are present in quiescent NSCs (qNSCs) in the subventricular zone of the mouse brain, but it remains largely unknown how lysosomal function is involved in the quiescence. Here we show that qNSCs exhibit higher lysosomal activity and degrade activated EGF receptor by endolysosomal degradation more rapidly than proliferating NSCs. Chemical inhibition of lysosomal degradation in qNSCs prevents degradation of signaling receptors resulting in exit from quiescence. Furthermore, conditional knockout of TFEB, a lysosomal master regulator, delays NSCs quiescence in vitro and increases NSC proliferation in the dentate gyrus of mice. Taken together, our results demonstrate that enhanced lysosomal degradation is an important regulator of qNSC maintenance.
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spelling pubmed-68844602019-12-03 Enhanced lysosomal degradation maintains the quiescent state of neural stem cells Kobayashi, Taeko Piao, Wenhui Takamura, Toshiya Kori, Hiroshi Miyachi, Hitoshi Kitano, Satsuki Iwamoto, Yumiko Yamada, Mayumi Imayoshi, Itaru Shioda, Seiji Ballabio, Andrea Kageyama, Ryoichiro Nat Commun Article Quiescence is important for sustaining neural stem cells (NSCs) in the adult brain over the lifespan. Lysosomes are digestive organelles that degrade membrane receptors after they undergo endolysosomal membrane trafficking. Enlarged lysosomes are present in quiescent NSCs (qNSCs) in the subventricular zone of the mouse brain, but it remains largely unknown how lysosomal function is involved in the quiescence. Here we show that qNSCs exhibit higher lysosomal activity and degrade activated EGF receptor by endolysosomal degradation more rapidly than proliferating NSCs. Chemical inhibition of lysosomal degradation in qNSCs prevents degradation of signaling receptors resulting in exit from quiescence. Furthermore, conditional knockout of TFEB, a lysosomal master regulator, delays NSCs quiescence in vitro and increases NSC proliferation in the dentate gyrus of mice. Taken together, our results demonstrate that enhanced lysosomal degradation is an important regulator of qNSC maintenance. Nature Publishing Group UK 2019-11-29 /pmc/articles/PMC6884460/ /pubmed/31784517 http://dx.doi.org/10.1038/s41467-019-13203-4 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Kobayashi, Taeko
Piao, Wenhui
Takamura, Toshiya
Kori, Hiroshi
Miyachi, Hitoshi
Kitano, Satsuki
Iwamoto, Yumiko
Yamada, Mayumi
Imayoshi, Itaru
Shioda, Seiji
Ballabio, Andrea
Kageyama, Ryoichiro
Enhanced lysosomal degradation maintains the quiescent state of neural stem cells
title Enhanced lysosomal degradation maintains the quiescent state of neural stem cells
title_full Enhanced lysosomal degradation maintains the quiescent state of neural stem cells
title_fullStr Enhanced lysosomal degradation maintains the quiescent state of neural stem cells
title_full_unstemmed Enhanced lysosomal degradation maintains the quiescent state of neural stem cells
title_short Enhanced lysosomal degradation maintains the quiescent state of neural stem cells
title_sort enhanced lysosomal degradation maintains the quiescent state of neural stem cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6884460/
https://www.ncbi.nlm.nih.gov/pubmed/31784517
http://dx.doi.org/10.1038/s41467-019-13203-4
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