Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1
Autor: | Shinpei Tamaki, Yasuhito Tokumoto, Yasuaki Kabe, Makoto Suematsu, Keiyo Takubo |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Thyroid Hormones Science Cellular differentiation Population Cell Culture Techniques Kruppel-Like Transcription Factors Biology Article Mice 03 medical and health sciences chemistry.chemical_compound Animals Progenitor cell education Cells Cultured Cell Proliferation Cyclin-Dependent Kinase Inhibitor p15 Oligodendrocyte Precursor Cells education.field_of_study Multidisciplinary Cell Differentiation Cell cycle Cell Hypoxia Rats Cell biology stomatognathic diseases KLF9 030104 developmental biology Animals Newborn nervous system RUNX1 chemistry Cell culture Core Binding Factor Alpha 2 Subunit Immunology Medicine Signal transduction Signal Transduction |
Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-15 (2017) Scientific Reports |
ISSN: | 2045-2322 |
DOI: | 10.1038/s41598-017-01023-9 |
Popis: | 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. |
Databáze: | OpenAIRE |
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