Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1 /631/136/532/2443 /631/532/2443 /13 /13/100 /13/106 /38 /38/89 /38/39 /42 /42/44 /96 article

Yasuhito Tokumoto, Shinpei Tamaki, Yasuaki Kabe, Keiyo Takubo, Makoto Suematsu

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Article number1019
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 2017 Dec 1

Fingerprint

Oligodendroglia
Thyroid Hormones
Adult Stem Cells
Core Binding Factor Alpha 2 Subunit
Cyclin-Dependent Kinase Inhibitor p15
Stem Cells
Central Nervous System
Hypoxia
Cell Hypoxia
Deceleration
Cultured Cells
Rodentia
Cell Cycle
Phenotype

ASJC Scopus subject areas

  • General

Cite this

Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1 /631/136/532/2443 /631/532/2443 /13 /13/100 /13/106 /38 /38/89 /38/39 /42 /42/44 /96 article. / Tokumoto, Yasuhito; Tamaki, Shinpei; Kabe, Yasuaki; Takubo, Keiyo; Suematsu, Makoto.

In: Scientific Reports, Vol. 7, No. 1, 1019, 01.12.2017.

Research output: Contribution to journalArticle

@article{59273c16698045dbbc663ad99efabc6f,
title = "Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1 /631/136/532/2443 /631/532/2443 /13 /13/100 /13/106 /38 /38/89 /38/39 /42 /42/44 /96 article",
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.",
author = "Yasuhito Tokumoto and Shinpei Tamaki and Yasuaki Kabe and Keiyo Takubo and Makoto Suematsu",
year = "2017",
month = "12",
day = "1",
doi = "10.1038/s41598-017-01023-9",
language = "English",
volume = "7",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1 /631/136/532/2443 /631/532/2443 /13 /13/100 /13/106 /38 /38/89 /38/39 /42 /42/44 /96 article

AU - Tokumoto, Yasuhito

AU - Tamaki, Shinpei

AU - Kabe, Yasuaki

AU - Takubo, Keiyo

AU - Suematsu, Makoto

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85018187812&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018187812&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-01023-9

DO - 10.1038/s41598-017-01023-9

M3 - Article

C2 - 28432293

AN - SCOPUS:85018187812

VL - 7

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 1019

ER -