Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1

Abstract The adult mammalian central nervous system (CNS) contains a population of slowly dividing oligodendrocyte precursor cells (OPCs), i.e., adult OPCs, which supply new oligodendrocytes throughout the life of animal. While adult OPCs develop from rapidly dividing perinatal OPCs, the mechanisms...

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Autores principales:	Yasuhito Tokumoto, Shinpei Tamaki, Yasuaki Kabe, Keiyo Takubo, Makoto Suematsu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a1d8461257554399bdc9e55ca6b4a59c
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spelling	oai:doaj.org-article:a1d8461257554399bdc9e55ca6b4a59c2021-12-02T11:53:08ZQuiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx110.1038/s41598-017-01023-92045-2322https://doaj.org/article/a1d8461257554399bdc9e55ca6b4a59c2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01023-9https://doaj.org/toc/2045-2322Abstract The adult mammalian central nervous system (CNS) contains a population of slowly dividing oligodendrocyte precursor cells (OPCs), i.e., adult OPCs, which supply new oligodendrocytes throughout the life of animal. While adult OPCs develop from rapidly dividing perinatal OPCs, the mechanisms underlying their quiescence remain unknown. Here, we show that perinatal rodent OPCs cultured with thyroid hormone (TH) under hypoxia become quiescent and acquire adult OPCs-like characteristics. The cyclin-dependent kinase inhibitor p15/INK4b plays crucial roles in the TH-dependent cell cycle deceleration in OPCs under hypoxia. Klf9 is a direct target of TH-dependent signaling. Under hypoxic conditions, hypoxia-inducible factors mediates runt-related transcription factor 1 activity to induce G1 arrest in OPCs through enhancing TH-dependent p15/INK4b expression. As adult OPCs display phenotypes of adult somatic stem cells in the CNS, the current results shed light on environmental requirements for the quiescence of adult somatic stem cells during their development from actively proliferating stem/progenitor cells.Yasuhito TokumotoShinpei TamakiYasuaki KabeKeiyo TakuboMakoto SuematsuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yasuhito Tokumoto Shinpei Tamaki Yasuaki Kabe Keiyo Takubo Makoto Suematsu Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1
description	Abstract The adult mammalian central nervous system (CNS) contains a population of slowly dividing oligodendrocyte precursor cells (OPCs), i.e., adult OPCs, which supply new oligodendrocytes throughout the life of animal. While adult OPCs develop from rapidly dividing perinatal OPCs, the mechanisms underlying their quiescence remain unknown. Here, we show that perinatal rodent OPCs cultured with thyroid hormone (TH) under hypoxia become quiescent and acquire adult OPCs-like characteristics. The cyclin-dependent kinase inhibitor p15/INK4b plays crucial roles in the TH-dependent cell cycle deceleration in OPCs under hypoxia. Klf9 is a direct target of TH-dependent signaling. Under hypoxic conditions, hypoxia-inducible factors mediates runt-related transcription factor 1 activity to induce G1 arrest in OPCs through enhancing TH-dependent p15/INK4b expression. As adult OPCs display phenotypes of adult somatic stem cells in the CNS, the current results shed light on environmental requirements for the quiescence of adult somatic stem cells during their development from actively proliferating stem/progenitor cells.
format	article
author	Yasuhito Tokumoto Shinpei Tamaki Yasuaki Kabe Keiyo Takubo Makoto Suematsu
author_facet	Yasuhito Tokumoto Shinpei Tamaki Yasuaki Kabe Keiyo Takubo Makoto Suematsu
author_sort	Yasuhito Tokumoto
title	Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1
title_short	Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1
title_full	Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1
title_fullStr	Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1
title_full_unstemmed	Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1
title_sort	quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate runx1
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a1d8461257554399bdc9e55ca6b4a59c
work_keys_str_mv	AT yasuhitotokumoto quiescenceofadultoligodendrocyteprecursorcellsrequiresthyroidhormoneandhypoxiatoactivaterunx1 AT shinpeitamaki quiescenceofadultoligodendrocyteprecursorcellsrequiresthyroidhormoneandhypoxiatoactivaterunx1 AT yasuakikabe quiescenceofadultoligodendrocyteprecursorcellsrequiresthyroidhormoneandhypoxiatoactivaterunx1 AT keiyotakubo quiescenceofadultoligodendrocyteprecursorcellsrequiresthyroidhormoneandhypoxiatoactivaterunx1 AT makotosuematsu quiescenceofadultoligodendrocyteprecursorcellsrequiresthyroidhormoneandhypoxiatoactivaterunx1
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Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1

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