2025-11-14 京都大学iPS細胞研究所
論文の概要図
<関連情報>
- https://www.cira.kyoto-u.ac.jp/j/pressrelease/news/251114-010000.html
- https://www.cell.com/stem-cell-reports/fulltext/S2213-6711(25)00318-2
加齢に伴うKAT7/HBO1活性の低下は免疫特性を促進することでimMKCLベースの血小板産生を阻害する Aging-dependent reduction of KAT7/HBO1 activity impairs imMKCL-based platelet production by promoting immune properties
Wei-Yin Qiu ∙ Sou Nakamura ∙ Sudip Kumar Paul ∙ … ∙ Naoshi Sugimoto ∙ Si Jing Chen ∙ Koji Eto
Stem Cell Reports November: 13, 2025
DOI:https://doi.org/10.1016/j.stemcr.2025.102714
Highlights
- Cell cycle regulation at proliferation stage determines platelet producibility
- Inhibition of KAT7 induces G0 arrest and immune phenotype dominance in imMKCLs
- The dominance of immune megakaryocytes is mediated by cGAS-STING pathway
- Pro-inflammatory cytokines released from imMKCLs could inhibit platelet production
Summary
The master cell bank (MCB) system is essential for regenerative cell therapy. We have developed induced pluripotent stem cell (iPSC)-based immortalized megakaryocyte progenitor cell lines (imMKCLs) as an MCB for iPSC-derived platelet (iPSC-PLT) transfusion. However, imMKCLs exhibit both thrombopoietic and immune-skewed properties, with enhanced immune activity impairing platelet production. The link between immune properties and thrombopoietic efficiency remains unclear. Here, we demonstrate that proliferating imMKCLs in G1 and G2/M interphases contribute to platelet generation, while lysine acetyltransferase 7 (KAT7) suppresses immune-biased dominancy to maintain these interphases. KAT7 inhibition with WM3835 increases G0 cells, mimicking imMKCL aging, and induces cGAS-STING activation, chromatin instability, and the secretion of tumor necrosis factor (TNF)-α, interferon (IFN)-β, and other pro-inflammatory cytokines. Additionally, TNF-α treatment recapitulates the transition to G0 seen with KAT7 loss. These findings identify KAT7 as a key regulator of imMKCL proliferation by preventing immune-skewed properties, highlighting its potential as a quality control marker in iPSC-PLT manufacturing.
