Novel Roles of Small Extracellular Vesicles in Regulating the Quiescence and Proliferation of Neural Stem Cells

Neural stem cell (NSC) quiescence plays pivotal roles in avoiding exhaustion of NSCs and securing sustainable neurogenesis in the adult brain. The maintenance of quiescence and transition between proliferation and quiescence are complex processes associated with multiple niche signals and environmen...

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Autores principales: Jingtian Zhang, Junki Uchiyama, Koshi Imami, Yasushi Ishihama, Ryoichiro Kageyama, Taeko Kobayashi
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Publicado: Frontiers Media S.A. 2021
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Acceso en línea:https://doaj.org/article/ca7cb6f4d83842bc9f362db59e4badb4
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spelling oai:doaj.org-article:ca7cb6f4d83842bc9f362db59e4badb42021-11-04T06:02:00ZNovel Roles of Small Extracellular Vesicles in Regulating the Quiescence and Proliferation of Neural Stem Cells2296-634X10.3389/fcell.2021.762293https://doaj.org/article/ca7cb6f4d83842bc9f362db59e4badb42021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.762293/fullhttps://doaj.org/toc/2296-634XNeural stem cell (NSC) quiescence plays pivotal roles in avoiding exhaustion of NSCs and securing sustainable neurogenesis in the adult brain. The maintenance of quiescence and transition between proliferation and quiescence are complex processes associated with multiple niche signals and environmental stimuli. Exosomes are small extracellular vesicles (sEVs) containing functional cargos such as proteins, microRNAs, and mRNAs. The role of sEVs in NSC quiescence has not been fully investigated. Here, we applied proteomics to analyze the protein cargos of sEVs derived from proliferating, quiescent, and reactivating NSCs. Our findings revealed fluctuation of expression levels and functional clusters of gene ontology annotations of differentially expressed proteins especially in protein translation and vesicular transport among three sources of exosomes. Moreover, the use of exosome inhibitors revealed exosome contribution to entrance into as well as maintenance of quiescence. Exosome inhibition delayed entrance into quiescence, induced quiescent NSCs to exit from the G0 phase of the cell cycle, and significantly upregulated protein translation in quiescent NSCs. Our results suggest that NSC exosomes are involved in attenuating protein synthesis and thereby regulating the quiescence of NSCs.Jingtian ZhangJingtian ZhangJunki UchiyamaKoshi ImamiKoshi ImamiYasushi IshihamaRyoichiro KageyamaRyoichiro KageyamaRyoichiro KageyamaTaeko KobayashiTaeko KobayashiFrontiers Media S.A.articleexosomesneural stem cellsproteomicsquiescenceproliferationsmall extracellular vesiclesBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution DOAJ
collection DOAJ
language EN
topic exosomes
neural stem cells
proteomics
quiescence
proliferation
small extracellular vesicles
Biology (General)
QH301-705.5
spellingShingle exosomes
neural stem cells
proteomics
quiescence
proliferation
small extracellular vesicles
Biology (General)
QH301-705.5
Jingtian Zhang
Jingtian Zhang
Junki Uchiyama
Koshi Imami
Koshi Imami
Yasushi Ishihama
Ryoichiro Kageyama
Ryoichiro Kageyama
Ryoichiro Kageyama
Taeko Kobayashi
Taeko Kobayashi
Novel Roles of Small Extracellular Vesicles in Regulating the Quiescence and Proliferation of Neural Stem Cells
description Neural stem cell (NSC) quiescence plays pivotal roles in avoiding exhaustion of NSCs and securing sustainable neurogenesis in the adult brain. The maintenance of quiescence and transition between proliferation and quiescence are complex processes associated with multiple niche signals and environmental stimuli. Exosomes are small extracellular vesicles (sEVs) containing functional cargos such as proteins, microRNAs, and mRNAs. The role of sEVs in NSC quiescence has not been fully investigated. Here, we applied proteomics to analyze the protein cargos of sEVs derived from proliferating, quiescent, and reactivating NSCs. Our findings revealed fluctuation of expression levels and functional clusters of gene ontology annotations of differentially expressed proteins especially in protein translation and vesicular transport among three sources of exosomes. Moreover, the use of exosome inhibitors revealed exosome contribution to entrance into as well as maintenance of quiescence. Exosome inhibition delayed entrance into quiescence, induced quiescent NSCs to exit from the G0 phase of the cell cycle, and significantly upregulated protein translation in quiescent NSCs. Our results suggest that NSC exosomes are involved in attenuating protein synthesis and thereby regulating the quiescence of NSCs.
format article
author Jingtian Zhang
Jingtian Zhang
Junki Uchiyama
Koshi Imami
Koshi Imami
Yasushi Ishihama
Ryoichiro Kageyama
Ryoichiro Kageyama
Ryoichiro Kageyama
Taeko Kobayashi
Taeko Kobayashi
author_facet Jingtian Zhang
Jingtian Zhang
Junki Uchiyama
Koshi Imami
Koshi Imami
Yasushi Ishihama
Ryoichiro Kageyama
Ryoichiro Kageyama
Ryoichiro Kageyama
Taeko Kobayashi
Taeko Kobayashi
author_sort Jingtian Zhang
title Novel Roles of Small Extracellular Vesicles in Regulating the Quiescence and Proliferation of Neural Stem Cells
title_short Novel Roles of Small Extracellular Vesicles in Regulating the Quiescence and Proliferation of Neural Stem Cells
title_full Novel Roles of Small Extracellular Vesicles in Regulating the Quiescence and Proliferation of Neural Stem Cells
title_fullStr Novel Roles of Small Extracellular Vesicles in Regulating the Quiescence and Proliferation of Neural Stem Cells
title_full_unstemmed Novel Roles of Small Extracellular Vesicles in Regulating the Quiescence and Proliferation of Neural Stem Cells
title_sort novel roles of small extracellular vesicles in regulating the quiescence and proliferation of neural stem cells
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/ca7cb6f4d83842bc9f362db59e4badb4
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