3 Modeling Human Thymic Development and Regenerating Thymic Function Using iPSC Technology濱㟢 洋子京都大学 iPS細胞研究所京都大学 大学院医学研究科免疫生物学1. iPS 細胞を活用したヒト胸腺発生の理解と機能再生T cells play a central role in immune responses to viral infections and cancers, and their development crucially depends on the thymus. Notably, thymic function begins to decline early in life, which may contribute to age-related T-cell dysfunction. Thymic epithelial cells (TECs), the major stromal component of the thymus, are essential for the development of self-MHC-restricted, self-tolerant naïve T cells with broad antigen reactivity. However, their remarkable heterogeneity and the inaccessibility of embryonic thymus tissue have long hindered our understanding of TEC development, particularly in humans.To address this, we have recently established a human iPSC-based model of thymus organogenesis in vitro using a simple 2D culture system. By mimicking embryonic signaling cues, our system generates FOXN1-expressing TEC progenitor-like cells and further gives rise to diverse mature TEC subtypes resembling those found in the human thymus, enabling us to infer their developmental trajectories. Moreover, upon co-culture with primary human thymocytes, these induced TECs support the generation of naïve T cells with diverse TCR repertoires. Our model offers a new framework for studying human thymus development and provides a potential platform for regenerative approaches to both congenital thymic deficiencies and age-related thymic involution.Center for iPS Cell Research and Application (CiRA)Laboratory of Immunobiology, Graduate School of Medicine, Kyoto University Yoko Hamazaki
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