Quiescence of adult oligodendrocyte precursor cells requires thyroid hormone and hypoxia to activate Runx1
Open accessAbstract
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.
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These previously uncharacterized temporal modules comprised oligodendrocyte lineage progression TFs and co-expression partners.
“These previously uncharacterized temporal modules comprised oligodendrocyte lineage progression TFs (e.g., Kcnip3, Olig2, Sox2, and Klf9; Maki et al., 2013; Marques et al., 2016; Tokumoto et al., 2017; Wu et al., 2012) and co-expression partners (e.g., Hes5, Eno1, Sox21, Purb, Zfp275, Foxj2, Zeb2, Tsc22d3, and Hopx; Figure 4F).”
From Single-Cell Analysis of Regional Differences in Adult V-SVZ Neural Stem Cell Lineages (2019) · cites this paper as Tokumoto et al., 2017
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References 67 · Cited by 16
- Authors
- Tokumoto, Y., Tamaki, S., Kabe, Y., Takubo, K., & Suematsu, M.
- Affiliations
- Keio University (JP)
- National Center for Global Health and Medicine (JP)
- Corresponding author
- Tokumoto, Yasuhito
- Suematsu, Makoto
- Venue
- Scientific Reports
- Published
- 2017-04-21
- Volume
- 7
- Issue
- 1
- Pages
- 1019-1019
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5430791
- OpenAlex
- W2605588696
- Cited by
- 16
- References
- 67
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 1
- FWCI
- 0.58
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Japan Agency for Medical Research and Development
- Keio University
- Japan Society for the Promotion of Science (15K07011, 16K15507, 26115005, 15H04861)
- Core Research for Evolutional Science and Technology
- Exploratory Research for Advanced Technology
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Neonatal and fetal brain pathology
- Keywords
- oligodendrocyte precursor cells, thyroid hormones, hypoxia, RUNX1, KLF9, hypoxia-inducible factor, G1 cell cycle arrest, oligodendrocyte development
- MeSH terms
- Oligodendrocyte Precursor Cells, Animals, Animals, Newborn, Cell Differentiation, Cells, Cultured, Thyroid Hormones, Signal Transduction, Cell Hypoxia, Cell Culture Techniques, Cell Proliferation, Core Binding Factor Alpha 2 Subunit, Cyclin-Dependent Kinase Inhibitor p15, Mice, Rats, Kruppel-Like Transcription Factors
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