2025-10-31 京都大学
<関連情報>
- https://www.kyoto-u.ac.jp/ja/research-news/2025-10-31-0
- https://www.kyoto-u.ac.jp/sites/default/files/2025-10/2510_StemCellRep_Maki_relj_web-703a035c681f8a16ff442e83178b834f.pdf
- https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(25)00291-7
最適化細胞治療のための低酸素状態が調整する脳卒中後オリゴデンドロサイト前駆細胞の変化特性解析 Characterizing hypoxia-orchestrated post-stroke changes in oligodendrocyte precursor cells for optimized cell therapy
Yasuhiro Kuwata ∙ Ken Yasuda ∙ Kazuto Tsukita ∙ … ∙ Ryosuke Takahashi ∙ Riki Matsumoto ∙ Takakuni Maki
Stem Cell Reports Published:October 30, 2025
DOI:https://doi.org/10.1016/j.stemcr.2025.102687
Highlights
- Hypoxia dynamically alters oligodendrocyte precursor cell (OPC) phenotypes post stroke
- OPCs under mild hypoxia acquire “oligogenic” transcriptional profile
- Severe hypoxia induces “angiogenic” OPC states detrimental for repair
- Hypoxia-modulated OPC traits guide optimal selection for cell therapy in stroke
Summary
Oligodendrocyte precursor cells (OPCs) are highly adaptable, engaging in diverse functions beyond myelination. However, how OPCs adjust their roles after ischemic stroke and contribute to recovery remains largely unknown. To address this gap, we constructed a “transient middle cerebral artery occlusion (tMCAO) atlas” by integrating mouse single-cell RNA sequencing (scRNA-seq) datasets and combined it with ex vivo OPC cultures and in vivo cell transplantation experiments. This approach revealed the emergence of “angiogenic” OPCs in the subacute phase and “oligogenic” OPCs in the chronic phase, driven by distinct levels of hypoxia—severe hypoxia inducing angiogenic OPCs and mild hypoxia promoting oligogenic OPCs. Ex vivo, severe hypoxic preconditioning faithfully induced angiogenic OPCs, and their intravenous transplantation enhanced angiogenesis and improved recovery in tMCAO mice. These findings highlight “oxygen tone” as a key regulator of OPC dynamic adaptation after ischemic stroke, offering a promising strategy to harness OPCs for stroke cell therapy.
